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1.
Exp Eye Res ; 243: 109900, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636803

RESUMO

A pterygium is a wedge-shaped fibrovascular growth of the conjunctiva membrane that extends onto the cornea, which is the outer layer of the eye. It is also known as surfer's eye. Growth of a pterygium can also occur on the either side of the eye, attaching firmly to the sclera. Pterygia are one of the world's most common ocular diseases. However, the pathogenesis remains unsolved to date. As the pathogenesis of pterygium is closely related to finding the ideal treatment, a clear understanding of the pathogenesis will lead to better treatment and lower the recurrence rate, which is notably high and more difficult to treat than a primary pterygium. Massive studies have recently been conducted to determine the exact causes and mechanism of pterygia. We evaluated the pathogenetic factors ultraviolet radiation, viral infection, tumor suppressor genes p53, growth factors, oxidative stress, apoptosis and neuropeptides in the progression of the disease. The heightened expression of TRPV1 suggests its potential contribution in the occurrence of pterygium, promoting its inflammation and modulating sensory responses in ocular tissues. Subsequently, the developmental mechanism of pterygium, along with its correlation with dry eye disease is proposed to facilitate the identification of pathogenetic factors for pterygia, contributing to the advancement of understanding in this area and may lead to improved surgical outcomes.


Assuntos
Pterígio , Pterígio/etiologia , Pterígio/metabolismo , Humanos , Fatores de Risco , Estresse Oxidativo , Raios Ultravioleta/efeitos adversos , Apoptose , Túnica Conjuntiva/patologia
2.
Mol Biol Rep ; 51(1): 524, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630344

RESUMO

BACKGROUND: Pterygium, characterized by the abnormal proliferation of epithelial cells, matrix remodeling, vascularization, and lesion migration, is a prevalent ocular surface disease involving the growth of fibrovascular tissue on the cornea. Despite the unclear underlying causes of pterygium, numerous investigations have indicated the involvement of cell death pathways in the regulation of cell cycle dynamics. Consequently, the objective of this study was to assess the expression levels of necroptosis markers in individuals diagnosed with pterygium, aiming to shed light on the potential role of necroptosis in the pathogenesis of this condition. METHODS: This study aimed to investigate the expression patterns of receptor-interacting serine/threonine kinase 3 (RIPK3) and receptor-interacting serine/threonine kinase 1 (RIPK1) genes in pterygium tissues. 41 patients undergoing pterygium excision surgery were recruited. Resected pterygium samples and normal conjunctival tissues were collected, and RIPK3 and RIPK1 mRNA levels were measured using quantitative real-time PCR. RESULTS: Our findings reveal that the expression of RIPK3 is significantly increased in samples obtained from individuals with pterygium. However, no significant alterations were observed in the expression of RIPK1 in these samples. Results showed significantly higher RIPK3 expression in pterygium tissues compared to controls. Moreover, increased RIPK3 levels correlated negatively with pterygium recurrence rates. CONCLUSIONS: These findings suggest RIPK3 may play a protective role against pterygium recurrence through necroptosis.


Assuntos
Pterígio , Humanos , Túnica Conjuntiva/anormalidades , Expressão Gênica/genética , Pterígio/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Serina
3.
Graefes Arch Clin Exp Ophthalmol ; 262(3): 957-965, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37878035

RESUMO

PURPOSE: The aim of this study was to evaluate the expression of placental growth factor (PLGF), neuropilin-1 (NP-1), and neuropilin-2 (NP-2) molecules in primary pterygium tissue compared with normal conjunctival tissue. METHODS: The records of 42 patients who underwent excision surgery with autografts for primary pterygium (pterygium group) and 20 patients who underwent conjunctival nevus excision surgery (control group) in the same period were reviewed retrospectively. The samples obtained from the pterygium tissues in the pterygium group and the clean conjunctival tissues adjacent to the nevus in the control group were collected from the archive. Immunohistochemical stains of the primary antibodies-1/100 diluted PLGF, NP-1, and NP-2 (Abcam Cambridge Science Park, UK)-were applied to all groups. Staining intensities and the percentage of positive cells in epithelial, endothelial, stromal, and inflammatory cells were analyzed by an experienced pathologist. RESULTS: The positivity rates of PLGF and NP-2 expression in epithelial, endothelial, stromal, and inflammatory cells were found to be higher in the pterygium group than in the control group (PLGF: p < 0.001, p < 0.001, p = 0.001, and p < 0.001, respectively; NP-2: p < 0.001 for all). Staining intensities for PLGF and NP-2 were higher in the pterygium group than in the control group (PLGF: p < 0.001, p < 0.001, p = 0.005, and p < 0.001, respectively; NP-2: p < 0.001, p < 0.001, p = 0.001, and p < 0.001, respectively). However, no significant differences were found in any cell type in terms of NP-1 expression positivity rates (p = 0.730, p = 0.121, p = 0.524, and p = 0.624, respectively) or staining intensity (p = 0.716, p = 0.147, p = 0.147, and p = 0.780, respectively). CONCLUSION: PLGF and NP-2 levels were found to be higher in pterygium tissue, while there was no difference in NP-1. These results indicate the possible roles of NP-2 and PLGF in primary pterygium.


Assuntos
Túnica Conjuntiva , Nevo , Pterígio , Neoplasias Cutâneas , Humanos , Túnica Conjuntiva/anormalidades , Neuropilina-1 , Neuropilina-2 , Fator de Crescimento Placentário , Pterígio/diagnóstico , Pterígio/cirurgia , Estudos Retrospectivos
4.
BMC Ophthalmol ; 24(1): 7, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178053

RESUMO

BACKGROUND: To investigate the effect of different sizes of pterygium on the front and back corneal topography, refractive changes and aberrations in natural-light and low-light conditions. METHODS: Sixty subjects with unilateral primary nasal pterygium were enrolled in this study. All the patients' uncorrected, best spectacle-corrected visual acuity, corneal topographic aberration data in 3 mm and 7 mm areas were collected. The pterygium size was evaluated by the slit-lamp photography and Sirius Scheimpflug Analyzer. RESULTS: The front topographic astigmatism values, corneal total aberrations, and higher-order aberrations in 3 mm and 7 mm areas were higher in the pterygium group than those in the control group. The pterygium horizontal length and thickness were moderately to strongly correlated with astigmatism and RMS of aberrations, while pterygium vertical length showed no or just mild correlation with the corneal astigmatism and aberrations. Compared to the readings in 3 mm area, the front and back corneal astigmatism and aberrations were larger in 7 mm area. CONCLUSIONS: Pterygium led to visual impairment by inducing astigmatism and aberrations. In low-light condition, the visual function worsened due to increased corneal astigmatism values and aberrations.


Assuntos
Astigmatismo , Doenças da Córnea , Pterígio , Humanos , Pterígio/complicações , Pterígio/diagnóstico , Astigmatismo/diagnóstico , Acuidade Visual , Córnea , Topografia da Córnea
5.
Optom Vis Sci ; 101(1): 62-70, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890114

RESUMO

SIGNIFICANCE: This study found that the unique properties of tear film breakup process in eyes with pterygium, combined with ocular surface parameters, further revealed specific dynamic mechanism. It suggested that the thickness of pterygium was especially valuable in deciding the necessity of surgical management. PURPOSE: This study aimed to explore the dynamic mechanism of tear film instability in eyes with pterygium. METHODS: A paired-eye controlled cross-sectional study was conducted. Seventy-eight patients with nasal pterygium were enrolled. Fluorescein tear film breakup was observed. Several key parameters related to tear film quality were defined and analyzed, including total breakup area (mathematically derived from pixel size using MATLAB), breakup velocity, fluorescein breakup time, breakup location and pattern, tear meniscus height, score of fluorescein corneal staining, and meiboscore. RESULTS: With comparable tear meniscus height, score of fluorescein corneal staining, and meiboscore between paired eyes (p > 0.05), eyes with pterygium had shorter breakup time, larger breakup area, and faster breakup velocity (p < 0.05). In eyes with pterygium, a positive correlation between meiboscore and pterygium parameters including length, thickness, and size was observed (p > 0.001). As the thickness increased, difference of breakup time and area between paired eyes increased (p = 0.02 and 0.046). Eyes with pterygium had more fixed inferonasal breakup location and often presented as dimple break (60%), whereas random break was the most common in contralateral normal eyes (62%). A unique breakup pattern named pterygium-induced local dimple break was found. It displayed as an irregular but vertical line-like shape appearing after lipid layer spreading, which was adjacent to the lower margin of pterygium and presented with unique properties including inferonasal breakup location, local breakup area, shorten breakup time, and faster breakup velocity. CONCLUSIONS: Eyes with pterygium showed a unique tear film breakup process and novel breakup pattern named pterygium-induced local dimple break . Dynamic mechanism played a significant role in tear film instability of eyes with pterygium rather than aqueous deficiency and increased evaporation.


Assuntos
Túnica Conjuntiva/anormalidades , Síndromes do Olho Seco , Pterígio , Humanos , Pterígio/cirurgia , Estudos Transversais , Lágrimas , Fluoresceína
6.
Eye Contact Lens ; 50(4): 183-188, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305478

RESUMO

OBJECTIVE: The study received funding from Ocular Therapeutix, Inc., Bedford, MA.We undertook this study to compare the efficacy of intracanalicular dexamethasone 0.4 mg with topical prednisolone acetate (PA) 1% in controlling postoperative pain and inflammation in patients undergoing pterygium surgery. METHODS: This was an open-label, prospective, interventional, nonrandomized comparative trial. Thirty patients were assigned to one of the following groups: Group A [intracanalicular insert of 0.4 mg dexamethasone placed into upper and lower puncta during the procedure, followed by at postoperative month 1 visit institution of topical PA 1% twice daily × 2 weeks then once daily × 2 weeks] or Group B [nonintervention group with institution on postoperative day 1 topical PA 1% every 2 hours × 2 weeks then four times per day × 2 weeks then twice daily × 2 weeks then once daily × 2 weeks]. RESULTS: Fifteen cases and 15 controls were enrolled. There was no statistical difference in patient-reported pain or satisfaction between the case and control groups at 1 day; 1 week; and 1, 3, and 6 months postoperatively. There was no significant difference in time to an ocular hyperemia score of 0 between the two groups. There was no difference in the rate of corneal reepithelialization and recurrence rate (two controls). Nine eyes had transient ocular hypertension (seven cases and two controls). CONCLUSION: Intracanalicular dexamethasone 0.4 mg may reduce the medication burden for patients who need prolonged postoperative steroid therapy as is routine in the setting of pterygium surgery. It is a safe and effective alternative to PA 1% drops alone for postoperative control of pain and inflammation in pterygium surgery.


Assuntos
Pterígio , Humanos , Pterígio/cirurgia , Pterígio/tratamento farmacológico , Estudos Prospectivos , Inflamação/tratamento farmacológico , Esteroides , Dexametasona/efeitos adversos , Dor/induzido quimicamente , Dor/tratamento farmacológico
7.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732006

RESUMO

A pterygium is a common conjunctival degeneration and inflammatory condition. It grows onto the corneal surface or limbus, causing blurred vision and cosmetic issues. Ultraviolet is a well-known risk factor for the development of a pterygium, although its pathogenesis remains unclear, with only limited understanding of its hereditary basis. In this study, we collected RNA-seq from both pterygial tissues and conjunctival tissues (as controls) from six patients (a total of twelve biological samples) and retrieved publicly available data, including eight pterygium samples and eight controls. We investigated the intrinsic gene regulatory mechanisms closely linked to the inflammatory reactions of pterygiums and compared Asian (Korea) and the European (Germany) pterygiums using multiple analysis approaches from different perspectives. The increased expression of antioxidant genes in response to oxidative stress and DNA damage implies an association between these factors and pterygium development. Also, our comparative analysis revealed both similarities and differences between Asian and European pterygiums. The decrease in gene expressions involved in the three primary inflammatory signaling pathways-JAK/STAT, MAPK, and NF-kappa B signaling-suggests a connection between pathway dysfunction and pterygium development. We also observed relatively higher activity of autophagy and antioxidants in the Asian group, while the European group exhibited more pronounced stress responses against oxidative stress. These differences could potentially be necessitated by energy-associated pathways, specifically oxidative phosphorylation.


Assuntos
Inflamação , Fosforilação Oxidativa , Estresse Oxidativo , Pterígio , RNA-Seq , Pterígio/genética , Pterígio/metabolismo , Humanos , Estresse Oxidativo/genética , Inflamação/genética , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Masculino , Feminino , Regulação da Expressão Gênica , Pessoa de Meia-Idade , Transdução de Sinais/genética
8.
Int J Mol Sci ; 25(16)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39201366

RESUMO

Pterygium is often associated with chronic ultraviolet (UV) radiation exposure and characterized by the overgrowth of conjunctiva and extracellular matrix (ECM) remodeling. Notably, several studies in the skin have demonstrated that chronic UV radiation can upregulate Granzyme B (GrB) expression and increase ECM degradation. The aim of this study was to compare GrB expression between pterygium and healthy controls and to further link this GrB expression to mast cells. Post-mortem pterygium tissues and conjunctival tissues from age-matched controls were used to assess GrB expression via immunofluorescence and microscopy. We found a significantly higher density of GrB+ cells from pterygium specimens compared to healthy controls. Furthermore, many of the GrB+ cells in pterygium specimens co-expressed tryptase, a mast cell marker. These findings suggest a role for conjunctival mast cell-secreted GrB in the pathogenesis of pterygium and highlight GrB as a possible therapeutic target in delaying or halting pterygium progression.


Assuntos
Túnica Conjuntiva , Granzimas , Pterígio , Humanos , Pterígio/metabolismo , Pterígio/patologia , Granzimas/metabolismo , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Mastócitos/metabolismo , Adulto , Estudos de Casos e Controles , Idoso de 80 Anos ou mais , Triptases/metabolismo
9.
Int Ophthalmol ; 44(1): 65, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347311

RESUMO

OBJECTIVES: To investigate the effects of subconjunctival injectable platelet-rich fibrin (i-PRF) injection on healing and complication rates after pterygium surgery with conjunctival autograft. METHODS: This retrospective and comparative study evaluated 31 eyes that received i-PRF injections under the donor and graft conjunctiva following pterygium surgery, while 34 eyes did not receive i-PRF after the pterygium surgery. The patients' follow-up period was for 12 months. Postoperative recurrence, epithelial healing time, postoperative pain score, graft edema, and sliding of the graft (need for re-suturation) data were evaluated. RESULTS: For the 12 months after surgery, one eye (3.2%) in the i-PRF group had developed corneal recurrence, and five eyes (14.7%) in the non-i-PRF group had developed recurrence. The mean corneal epithelial healing time was 2.96 ± 0.70 days in the i-PRF group and 3.58 ± 0.70 days in the non-i-PRF group (p = 0.001). The mean healing time of the donor conjunctiva epithelium was 3.84 ± 0.70 days in the i-PRF group, whereas it was 4.44 ± 0.74 days in the non-i-PRF group (p = 0.006). The mean postoperative pain score was 4.45 ± 1.52 in the i-PRF group and 5.08 ± 1.40 in the non-i-PRF group. In the non-i-PRF group, three cases (8.8%) required re-suturation, whereas, in the i-PRF group, no one required re-suturation. CONCLUSIONS: Thanks to its platelets-derived growth factors, i-PRF can be a safe and effective adjuvant therapy for faster healing of conjunctival autograft and in the prevention of recurrence.


Assuntos
Fibrina Rica em Plaquetas , Pterígio , Humanos , Pterígio/cirurgia , Autoenxertos , Estudos Retrospectivos , Resultado do Tratamento , Seguimentos , Túnica Conjuntiva/transplante , Transplante Autólogo , Dor Pós-Operatória , Recidiva , Complicações Pós-Operatórias/prevenção & controle
10.
Int Ophthalmol ; 44(1): 297, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951293

RESUMO

BACKGROUND/OBJECTIVES: To evaluate the effect of topical cyclosporine A (CsA) 0.05% in patients with pterygium surgery using fibrin glue (FG). SUBJECTS/METHODS: Patients with primary nasal pterygium were retrospectically analyzed and categorized into two groups: Group 1 with 41 eyes from 38 patients as a control group and group 2 with 39 eyes from 36 patients who received topical CsA twice a day for 6 months. Patients were assessed for recurrence rate, tear film parameters, side effects, and complications at postoperative intervals of 1-7 days; 1st, 3rd, 6th and 12th months. The follow-up period was 1 year. RESULTS: The two groups were age (p = 0.934) and sex (p = 0.996) matched. CsA drop was discontinued in one patient due to burning sensation and conjunctival hyperemia after 1 week. There was no statistically significant difference between the mean preoperative and postoperative 1st year Schirmer I and tear break-up time (TBUT) values in group 1 (p = 0.136; p = 0.069). Although the difference between the mean preoperative and postoperative 1st year TBUT values in group 2 was not statistically different (p = 0.249), Schirmer I results were higher postoperatively (p = 0.003). There was no statistically significant difference between preoperative Schirmer (p = 0.496), postoperative Schirmer (p = 0.661), preoperative TBUT (p = 0.240) and postoperative TBUT (p = 0.238) results of the two groups. Recurrence was observed in only one patient from group 1. CONCLUSION: No recurrent pterygium cases were observed in group 2. Schirmer I values were higher postoperatively in group 2; thus,topical CsA treatment may improve lacrimal secretion and be effective after pterygium surgery with FG.


Assuntos
Ciclosporina , Adesivo Tecidual de Fibrina , Imunossupressores , Pterígio , Humanos , Pterígio/cirurgia , Pterígio/diagnóstico , Ciclosporina/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Adesivo Tecidual de Fibrina/administração & dosagem , Imunossupressores/administração & dosagem , Estudos Retrospectivos , Seguimentos , Adulto , Adesivos Teciduais/administração & dosagem , Adesivos Teciduais/uso terapêutico , Resultado do Tratamento , Idoso , Soluções Oftálmicas/administração & dosagem , Procedimentos Cirúrgicos Oftalmológicos/métodos , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Recidiva , Túnica Conjuntiva , Lágrimas/metabolismo , Lágrimas/fisiologia
11.
Int Ophthalmol ; 44(1): 63, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347388

RESUMO

PURPOSE: Pterygium is a hyaline degenerative disease of the conjunctiva characterized by the progression of fibrovascular connective tissue from the bulbar conjunctiva to the cornea. The mechanism of pterygium formation is still not fully understood. Transient receptor potential (TRP) channels are a group of ion channels with distinct characteristics. Recent indications suggest TRP channels may play a significant regulatory role in pterygium development, but previous studies have mainly focused on in silico analysis. Accordingly, in the present study, we aimed to decipher the expression signatures and role of TRP channels in pterygium development. METHODS: The study encompassed a cohort of 45 patients matched for age and gender distribution, comprising 30 individuals with primary pterygium (PP) and 15 individuals with recurrent pterygium (RP). The control group consisted of unaffected conjunctival tissue obtained from the same set of patients. High-throughput screening of differentially expressed TRP channels in pterygium tissues was achieved with the help of Fluidigm 96.96 Dynamic Array Expression Chip and reactions were held in BioMark™ HD System Real-Time PCR platform. RESULTS: Statistically significant increases were found in the expression of 21 genes, mainly TRPA1 (p = 0.021), TRPC2 (p = 0.001), and TRPM8 (p = 0.003), in patients with PP, and in TRPC5 (p = 0.05), TRPM2 (p = 0.029), TRPM4 (p = 0.03), TRPM6 (p = 0.045), TRPM8 (p = 0.038), TRPV1 (p = 0.01) and TRPV4 (p = 0.025) genes in RP tissues. CONCLUSION: Collectively, TRP channel proteins appear to play pivotal roles in both the development and progression of pterygium, making them promising candidates for future therapeutic interventions in patients afflicted by this condition.


Assuntos
Túnica Conjuntiva/anormalidades , Pterígio , Canais de Potencial de Receptor Transitório , Humanos , Canais de Potencial de Receptor Transitório/genética , Canais de Potencial de Receptor Transitório/metabolismo , Pterígio/diagnóstico , Ensaios de Triagem em Larga Escala , Túnica Conjuntiva/metabolismo
12.
Turk J Med Sci ; 54(4): 675-681, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39295613

RESUMO

Background/aim: To compare the efficacy of topical 0.05% cyclosporine A (CsA) and 0.1% topical cyclosporine A (CsA) over a 6-month period following pterygium surgery, specifically evaluating their effects on postoperative recurrence and clinical parameters. Material and methods: This clinical study enrolled 245 patients with pterygium who underwent surgery using the conjunctival autograft technique with mitomycin C (MMC) were enrolled. Participants were divided into three groups: Group 1 (0.05% CsA) (n = 80), Group 2 (0.1% CsA) (n = 80), and a control group (n = 85). They were examined at postoperative first day, first week, first month and sixth month. The examination included best corrected visual acuity (BCVA), intraocular pressure (IOP), presence of inflammation, and ptergium recurrence, all of which were compared across the groups. Results: The mean age of the patients was 63.22 ± 9.39 years, with 53.3% male and 46.7% female. The three groups were similar in terms of demographic characteristics and pterygium size. Inflammation in surgical area significantly regressed in all groups at 6 months postoperatively (p < 0.05). Inflammation in the first and sixth months was not different between the groups (p = 0.118, p = 0.580, and p = 0.435, respectively). The recurrence rate was not different between groups (p = 0.890). There was no statistically significant difference between groups regarding IOP (p = 0.818). A significant increase in BCVA after surgery was observed in three groups compared to preoperative levels (p < 0.05). Conclusion: This study showed that there was no difference between the efficacy of 6 month topical 0.05% CsA and 0.1% CsA application after pterygium surgery with the conjunctival autograft technique with MMC on postoperative outcomes. Including postoperative recurrence, IOP changes, BCVA changes and surgical area inflammation.


Assuntos
Ciclosporina , Pterígio , Recidiva , Humanos , Pterígio/cirurgia , Pterígio/tratamento farmacológico , Feminino , Masculino , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Pessoa de Meia-Idade , Idoso , Administração Tópica , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/transplante , Resultado do Tratamento , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Acuidade Visual/efeitos dos fármacos , Soluções Oftálmicas/administração & dosagem , Pressão Intraocular/efeitos dos fármacos
13.
Vestn Oftalmol ; 140(2. Vyp. 2): 136-142, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38739143

RESUMO

Pterygium is a common inflammatory-proliferative disease characterized by the invasion of degeneratively altered fibrovascular tissue into the cornea. This literature review analyzes the etiological factors and pathogenetic concepts of its development, describes modern methods of diagnostics and surgical treatment of pterygium, and pays particular attention to the assessment of structural and functional changes in the cornea occurring during the growth of pterygium and after its excision.


Assuntos
Procedimentos Cirúrgicos Oftalmológicos , Pterígio , Pterígio/diagnóstico , Pterígio/terapia , Pterígio/etiologia , Humanos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Córnea/diagnóstico por imagem , Córnea/patologia , Túnica Conjuntiva/patologia
14.
Hum Mol Genet ; 30(1): 72-77, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33450762

RESUMO

Ocular pterygium-digital keloid dysplasia (OPDKD) presents in childhood with ingrowth of vascularized connective tissue on the cornea leading to severely reduced vision. Later the patients develop keloids on digits but are otherwise healthy. The overgrowth in OPDKD affects body parts that typically have lower temperature than 37°C. We present evidence that OPDKD is associated with a temperature sensitive, activating substitution, p.(Asn666Tyr), in PDGFRB. Phosphorylation levels of PDGFRB and downstream targets were higher in OPDKD fibroblasts at 37°C but were further greatly increased at the average corneal temperature of 32°C. This suggests that the substitution cause significant constitutive autoactivation mainly at lower temperature. In contrast, a different substitution in the same codon, p.(Asn666Ser), is associated with Penttinen type of premature aging syndrome. This devastating condition is characterized by widespread tissue degeneration, including pronounced chronic ulcers and osteolytic resorption in distal limbs. In Penttinen syndrome fibroblasts, equal and high levels of phosphorylated PDGFRB was present at both 32°C and 37°C. This indicates that this substitution causes severe constitutive autoactivation of PDGFRB regardless of temperature. In line with this, most downstream targets were not affected by lower temperature. However, STAT1, important for tissue wasting, did show further increased phosphorylation at 32°C. Temperature-dependent autoactivation offers an explanation to the strikingly different clinical outcomes of substitutions in the Asn666 codon of PDGFRB.


Assuntos
Acro-Osteólise/genética , Túnica Conjuntiva/anormalidades , Deformidades Congênitas dos Membros/genética , Progéria/genética , Pterígio/genética , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética , Anormalidades da Pele/genética , Acro-Osteólise/diagnóstico por imagem , Acro-Osteólise/patologia , Adolescente , Adulto , Substituição de Aminoácidos/genética , Criança , Pré-Escolar , Túnica Conjuntiva/diagnóstico por imagem , Túnica Conjuntiva/patologia , Feminino , Humanos , Lactente , Deformidades Congênitas dos Membros/diagnóstico por imagem , Deformidades Congênitas dos Membros/patologia , Masculino , Mutação de Sentido Incorreto/genética , Fenótipo , Fosforilação/genética , Progéria/diagnóstico por imagem , Progéria/patologia , Pterígio/diagnóstico por imagem , Pterígio/patologia , Anormalidades da Pele/patologia , Temperatura , Adulto Jovem
15.
Exp Eye Res ; 233: 109522, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37271310

RESUMO

Pterygium is a common degenerative disease characterized by fibrovascular outgrowth towards cornea. Around 200 million people have been reported to be affected by the pterygium in the world. Although the risk factors for pterygium are well documented, the molecular pathogenesis of pterygium seems to be very complex and remains highly elusive. However, the common sense for the development of pterygium appears to be deregulation of growth hemostasis due to aberrant apoptosis. In addition, pterygium shares many features with human cancers, including dysregulation of apoptosis, persistent proliferation, inflammation, invasion, and relapse following resection. Cytochrome P450 (CYP) monooxygenases are a superfamily of heme-containing enzymes with a wide range of structural and functional diversity. In the present study, we aimed to identify significant expression signatures of CYP gene in pterygium. For the study, a total number of 45 patients (30 primary and 15 recurrent pterygium) were included. For the high-throughput screening of CYP gene expression, Fluidigm 96.96 Dynamic Array Expression Chip was used and analyzed with BioMark™ HD System Real-Time PCR system. Remarkably, CYP genes were identified to be significantly overexpressed in both primary and recurrent pterygium samples. Most prominent overexpression was observed in CYP1A1, CYP11B2 and CYP4F2 in primary pterygium and CYP11A1 and CYP11B2 in recurrent pterygium. Consequently, present findings suggest the significant involvement of CYP genes in the development and progression of pterygium.


Assuntos
Pterígio , Humanos , Pterígio/metabolismo , Ensaios de Triagem em Larga Escala , Citocromo P-450 CYP11B2 , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo
16.
Inflamm Res ; 72(3): 589-602, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36692516

RESUMO

OBJECTIVES: We aimed at identifying the role of transient receptor potential (TRP) channels in pterygium. METHODS: Based on microarray data GSE83627 and GSE2513, differentially expressed genes (DEGs) were screened and 20 hub genes were selected. After gene correlation analysis, 5 TRP-related genes were obtained and functional analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Multifactor regulatory network including mRNA, microRNAs (miRNAs) and transcription factors (TFs) was constructed. The 5 gene TRP signature for pterygium was validated by multiple machine learning (ML) programs including support vector classifiers (SVC), random forest (RF), and k-nearest neighbors (KNN). Additionally, we outlined the immune microenvironment and analyzed the candidate drugs. Finally, in vitro experiments were performed using human conjunctival epithelial cells (CjECs) to confirm the bioinformatics results. RESULTS: Five TRP-related genes (MCOLN1, MCOLN3, TRPM3, TRPM6, and TRPM8) were validated by ML algorithms. Functional analyses revealed the participation of lysosome and TRP-regulated inflammatory pathways. A comprehensive immune infiltration landscape and TFs-miRNAs-mRNAs network was studied, which indicated several therapeutic targets (LEF1 and hsa-miR-455-3p). Through correlation analysis, MCOLN3 was proposed as the most promising immune-related biomarker. In vitro experiments further verified the reliability of our in silico results and demonstrated that the 5 TRP-related genes could influence the proliferation and proinflammatory signaling in conjunctival tissue contributing to the pathogenesis of pterygium. CONCLUSIONS: Our study suggested that TRP channels played an essential role in the pathogenesis of pterygium. The identified pivotal biomarkers (especially MCOLN3) and pathways provide novel directions for future mechanistic and therapeutic studies for pterygium.


Assuntos
MicroRNAs , Pterígio , Canais de Potencial de Receptor Transitório , Humanos , Pterígio/genética , Canais de Potencial de Receptor Transitório/genética , Reprodutibilidade dos Testes , Túnica Conjuntiva , MicroRNAs/genética
17.
BMC Ophthalmol ; 23(1): 363, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37641016

RESUMO

BACKGROUND: Pterygium is a common ocular surface disease. Pterygium combined with corneal perforation is rare. CASE PRESENTATION: A 28-year-old female patient visited our outpatient clinic due to sudden onset of blurred vision and increased tearing in her left eye. The visual acuity was 1.0 OD and intraocular pressure (IOP) of 19.5 mmHg for the right eye with no significant abnormalities found in the anterior and posterior segments. The visual acuity of her left eye was 0.06, and IOP was 6.2 mmHg. A triangular vascular membranous tissue was seen in her left eye below the nose growing into the cornea and the pupil area was not touched. Slit-lamp examination revealed a tiny round corneal perforation in 8 o'clock position of the lesion area. Hospital diagnosis was given as pterygium combined with corneal perforation. The patient was treated with levofloxacin eye drops and autologous serum-based eye drops. CONCLUSIONS: We report a rare case of pterygium combined with corneal perforation. Perforation is a very rare complication of pterygium. This patient received proper treatment and good result was seen. This article aimed to improve clinicians' understanding of pterygium.


Assuntos
Perfuração da Córnea , Pterígio , Humanos , Feminino , Adulto , Pterígio/complicações , Pterígio/diagnóstico , Perfuração da Córnea/diagnóstico , Perfuração da Córnea/etiologia , Córnea , Soluções Oftálmicas
18.
BMC Ophthalmol ; 23(1): 175, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095479

RESUMO

BACKGROUND: Management of pterygium is dependent on the grading of pterygium and its clinical presentation (inflamed or quiescent), and surgical excision is the final choice of treatment for the pterygium extending beyond the limbus. Infectious keratitis is one of the most commonly reported complications in recent years. To the best of our knowledge, Klebsiella keratitis after pterygium surgery has not been described in the current literature. Here, we report a patient with corneal ulcer formation following pterygium surgical excision. CASE PRESENTATION: A 62-year-old woman presented with complaints of pain, blurred vision, photophobia and redness in her left eye for a month. She had a history of pterygium surgical excision two months ago. Slit-lamp examination showed conjunctival congestion, a central whitish corneal ulcer with a central epithelial defect, and hypopyon. Corneal scraped sample revealed multidrug resistant (MDR) Klebsiella pneumonia and the strain was found to be sensitive to cefoxitin and ciprofloxacin. Intracameral cefuroxime (1 mg/0.1 mL) injection, fortified cefuroxime ophthalmic suspension (50 mg/mL) and moxifloxacin ophthalmic suspension (0.5%) were successfully administered to control the infection. Since residual central stromal opacification remained persistent, final visual acuity did not improve beyond finger counting at two meters. CONCLUSIONS: Klebsiella keratitis is a rare and sight-threatening complication following pterygium excision. This report emphasizes the importance of close follow-up examination following pterygium surgeries.


Assuntos
Úlcera da Córnea , Ceratite , Pterígio , Humanos , Feminino , Pessoa de Meia-Idade , Úlcera da Córnea/tratamento farmacológico , Pterígio/cirurgia , Cefuroxima/uso terapêutico , Klebsiella , Transtornos da Visão
19.
BMC Ophthalmol ; 23(1): 145, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37029360

RESUMO

BACKGROUND: Severe ocular surface disorders are one of the major blinding diseases, and a paucity of original tissue obscures successful reconstruction. We developed a new surgical technique of direct oral mucosal epithelial transplantation (OMET) to reconstruct severely damaged ocular surfaces in 2011. This study elaborates on the clinical efficacy of OMET. METHODS: A retrospective review of patients with severe ocular surface disorders who underwent OMET from 2011 to 2021 at the Department of Ophthalmology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine was conducted. Patients who were followed up for at least 3 months postoperatively and had sufficient pre or postoperative records were included. Surgical efficacy was evaluated by comparing the best-corrected visual acuity (BCVA), corneal transparency, neovascularization grade, and symblepharon grade. Additionally, postoperative ocular surface impression cytology was used to study the morphology of the newborn epithelial cells. RESULTS: Forty-eight patients (49 eyes; mean age: 42.55 ± 12.40 years, range:12-66 years) were enrolled in the study. The etiology included chemical burns (30 eyes), thermal burns (16 eyes), explosive injuries (1 eye), Stevens-Johnson syndrome (1 eye), and multiple pterygiums (1 eye). The mean follow-up period was 25.97 ± 22.99 months. Postoperatively, 29 eyes (59.18%) showed improved corneal transparency, 26 eyes (53.06%) had improved BCVA, 47 eyes (95.92%) had a stable epithelium until the final follow-up, 44 eyes (89.80%) had a reduced neovascularization grade. Of the 20 eyes with preoperative symblepharon, 15 (75%) were completely resolved, and five (25%) were partially resolved. Impression cytological studies showed no postoperative conjunctival invasion onto the corneal surface. CONCLUSIONS: OMET is a safe and effective surgical technique for reconstruction in severe ocular surface disorder by maintaining a stable epithelium and reducing the neovascularization and symblepharon grade.


Assuntos
Queimaduras Químicas , Doenças da Córnea , Epitélio Corneano , Queimaduras Oculares , Limbo da Córnea , Pterígio , Recém-Nascido , Humanos , Adulto , Pessoa de Meia-Idade , Doenças da Córnea/cirurgia , Resultado do Tratamento , Mucosa Bucal , Córnea , Estudos Retrospectivos , Queimaduras Oculares/cirurgia
20.
Optom Vis Sci ; 100(3): 207-210, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36715995

RESUMO

SIGNIFICANCE: Mechanical factors are also associated with meibomian gland dysregulation in patients with pterygium. Dry eye parameters were assessed, and the results support the association between pterygium and dry eye disease. PURPOSE: This study aimed to investigate how meibomian gland dysfunction and dry eye parameters relate to the existence of pterygium. METHODS: Patients with pterygium and healthy volunteers of similar age and demographic characteristics were included. Schirmer 1 test, Ocular Surface Disease Index score, fluorescein tear film breakup time, and ocular surface staining scores (Oxford score) were recorded. Meiboscores were estimated based on meibomian gland loss rate on infrared meibography (SL-D701; Topcon, IJssel, the Netherlands). The symmetry of meibomian gland loss with respect to eyelid midline was assessed. RESULTS: Fifty-four eyes with pterygium (group 1) and 50 eyes of healthy volunteers (group 2) were included. The mean ages were 54.0 ± 12.3 and 52.3 ± 8.0 years, respectively. Schirmer 1 test results and tear film breakup time were lower in group 1 ( P = .007, P < .001). Oxford and Ocular Surface Disease Index scores were significantly higher in group 1 ( P = .009, P < .001). The mean meiboscores were significantly higher in group 1 ( P < .001). There was meibomian gland depletion in 90.7% (49 of 54) of group 1 and 32% (16 of 50) of group 2 ( P < .001). Meibomian gland loss region was distributed asymmetrically in 75.5% (37 of 49) of the eyes in group 1, but not in any of the eyes in group 2. The asymmetry was located on the side where the pterygium was detected in 94.5% (35 of 37) of these eyes. CONCLUSIONS: Meibomian glands are influenced morphologically and functionally in eyes with pterygium. The overlap of the pterygium location and meibomian gland abnormality suggests a direct mechanical relationship. In managing pterygium patients, the possibility of meibomian gland dysfunction and associated evaporative dry eye should be considered.


Assuntos
Síndromes do Olho Seco , Doenças Palpebrais , Disfunção da Glândula Tarsal , Pterígio , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Glândulas Tarsais , Pterígio/diagnóstico , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologia , Lágrimas , Doenças Palpebrais/diagnóstico
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