Risk factors for pterygium: Latest research progress on major pathogenesis.

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.

RIPK3 and RIPK1 gene expression in pterygium: unveiling molecular insights into pathogenesis.

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.

Comparison of postoperative topical interferon-α2b versus intraoperative mitomycin C for pterygium recurrence prevention: a randomized clinical trial.

PURPOSE: To evaluate the effect of postoperative interferon-alpha 2b (IFN-α2b) ophthalmic drops versus intraoperative mitomycin-c (MMC) on preventing pterygium recurrence. METHODS: This prospective randomized clinical trial was conducted on patients who were candidates for pterygium surgery. A total of 75 patients were included in the study from December 2021 to December 2022, of which 64 patients (one eye each) were examined and analyzed based on the inclusion criteria. Then the patients were randomly assigned to control groups, intra-operative MMC (32 patients) and the intervention group, IFN-α2b drops after the operation (32 patients). All patients underwent pterygium surgery using the rotational conjunctival flap method. RESULTS: In terms of pterygium grading, 8 (12.5%), 25 (39.06%), and 31 (48.44%) eyes were in grades 1, 2, and 3, respectively. The average size of the pterygium was 3.6 ± 0.7 mm. The grade and size of pterygium had the same distribution in the two groups. There was no statistically significant difference between the two groups in the level of post-operative clinical inflammation. The present study showed no significant difference in complications between the two groups (p = 0.999). The recurrence rate in the control group was 9.4% (3 eyes), and 0% (no recurrence) in the intervention group (p = 0.119). CONCLUSIONS: interferon-alpha 2b group did not show a statistically significant difference in preventing pterygium recurrence compared to the mitomycin C group. The post-surgery administration of IFN-α 2b drops can effectively prevent pterygium recurrence with a comparable and even more compelling effect than MMC during surgery.

The effect of different pterygium surgery techniques on the ocular surface parameters in different durations: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of different pterygium surgery techniques on ocular surface (OS) in different follow-up periods. METHODS: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and China Biology Medicine disc were searched for studies reporting pre- and post-operative OS parameters in pterygium. RESULTS: A total of 33 articles were finally included. Three OS parameters showed relatively consistent changing trends after surgery including ocular surface disease index (OSDI), tear film break-up time (BUT), and score of corneal fluorescein staining (SCFS). They worsened significantly at 1w post-operation and then gradually improved: OSDI and BUT showed obvious improvement in 1 m post-operation (SMD = - 0.58, 95%CI = [- 1.04, - 0.13]; SMD = 0.42, 95%CI = [0.06, 0.78]); SCFS was restored to preoperative levels in 3 m after surgery (SMD = - 0.54, 95%CI = [- 1.16, 0.07]). Another parameter, Schirmer test without anesthesia (SIT), presented transient increase at 1w post-operation (SMD = 0.87, 95%CI = [0.27, 1.47]) and presented a relatively stable improvement after 1 m post-operation (SMD = 0.52, 95%CI = [0.16, 0.89]). All parameters in amniotic membrane graft (AMT) showed better improvement in early stage and they showed non-inferior improvements in the long term compared with conjunctival autograft (CAG). Limbal-conjunctival autograft (LCAG) made excellent improvement to OS in the long term while pterygium excision (PE) showed the worst OS. The type of pterygium (primary and secondary), diabetes mellitus (DM) status, and fixation method had certain effects on the results. CONCLUSIONS: OS of pterygium is deteriorated at 1w post-operation then gradually improved to preoperative levels after 1 m post-operation. Among various surgery techniques, LCAG had the best improvement to OS which especially displayed in the long-term outcomes.

Expression of placental growth factor, neuropilin-1, and neuropilin-2 in primary pterygium tissue.

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.

The effect of pterygium on front and back corneal astigmatism and aberrations in natural-light and low-light conditions.

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.

Multi-System-Level Analysis with RNA-Seq on Pterygium Inflammation Discovers Association between Inflammatory Responses, Oxidative Stress, and Oxidative Phosphorylation.

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.

Comparative analysis of surgical treatment modalities for a popliteal pterygium: a meta-analysis.

INTRODUCTION: Popliteal pterygium syndrome is a rare congenital disorder characterized by orofacial, cutaneous, musculoskeletal, and genital anomalies. The popliteal pterygium (PP) affects ambulation due to severe knee flexion contracture and equinovarus deformities. Surgical treatment aims to correct these deformities while preserving limb sensibility. However, due to its rarity, surgical guidelines are lacking. MATERIALS AND METHODS: A meta-analysis according to PRISMA guidelines was conducted to summarize and compare surgical methods for PP. 183 paper were identified in PubMed and data from 32 articles were analyzed, including patient demographics, treatment modalities (Ilizarov fixator, femoral osteotomy, skin/soft tissue procedures, hamstring release, nerve surgery, and amputation), pre- and post-operative abilities to walk, knee joint parameters, complications, and recurrent contractions. RESULTS: Among 58 patients (87 limbs), Ilizarov fixator demonstrated improved knee and ankle mobility postoperatively, but showed a relatively high surgical session count and complication rates. Femoral osteotomy achieved successful knee posture correction with fewer sessions and no complications. Isolated skin/soft tissue procedures improved flexion contracture and mobility, though they required several procedures. Hamstring release achieved notable contracture reduction but also necessitated multiple interventions. Nerve surgery and amputation had limited data, warranting further investigation. CONCLUSION: The management of PP demands a comprehensive approach, considering individual patient characteristics and treatment outcomes. While different surgical modalities offer distinct benefits, a classification or guideline to treat this deformity is still lacking. Further research is essential to validate findings, refine treatment approaches, and enhance the quality of life for individuals with PP.

The effect of cyclosporine a in pterygium surgery using fibrin glue.

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.

Effects of injectable platelet-rich fibrin (i-PRF) on pterygium surgery with conjunctival autograft.

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.

High-throughput screening of transient receptor potential (TRP) channels in pterygium.

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.

[Current possibilities for the diagnosis and treatment of pterygium]. / Sovremennye vozmozhnosti diagnostiki i lecheniya pterigiuma.

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.

High-throughput screening of cytochrome P450 (CYP) family of genes in primary and recurrent pterygium.

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.

Uncovering the role of transient receptor potential channels in pterygium: a machine learning approach.

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.

Pterygium combined with corneal perforation: a case report.

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.

Multi-drug resistant Klebsiella-induced corneal ulcer following pterygium surgery: a case report.

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.

Key Genes of Immunity Associated with Pterygium and Primary Sjögren's Syndrome.

Pterygium and primary Sjögren's Syndrome (pSS) share many similarities in clinical symptoms and ocular pathophysiological changes, but their etiology is unclear. To identify the potential genes and pathways related to immunity, two published datasets, GSE2513 containing pterygium information and GSE176510 containing pSS information, were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of pterygium or pSS patients compared with healthy control conjunctiva, and the common DEGs between them were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted for common DEGs. The protein-protein interaction (PPI) network was constructed using the STRING database to find the hub genes, which were verified in clinical samples. There were 14 co-upregulated DEGs. The GO and KEGG analyses showed that these common DEGs were enriched in pathways correlated with virus infection, antigen processing and presentation, nuclear factor-kappa B (NF-κB) and Th17 cell differentiation. The hub genes (IL1R1, ICAM1, IRAK1, S100A9, and S100A8) were selected by PPI construction. In the era of the COVID-19 epidemic, the relationship between virus infection, vaccination, and the incidence of pSS and pterygium growth deserves more attention.

Synergic Action of Insulin-like Growth Factor-2 and miRNA-483 in Pterygium Pathogenesis.

Pterygium is a multifactorial disease in which UV-B is speculated to play a key role by inducing oxidative stress and phototoxic DNA damage. In search for candidate molecules that are useful for justifying the intense epithelial proliferation observed in pterygium, our attention has been focused on Insulin-like Growth Factor 2 (IGF-2), mainly detected in embryonic and fetal somatic tissues, which regulate metabolic and mitogenic functions. The binding between IGF-2 and its receptor Insulin-like Growth Factor 1 Receptor (IGF-1R) activates the PI3K-AKT pathway, which leads to the regulation of cell growth, differentiation, and the expression of specific genes. Since IGF2 is regulated by parental imprinting, in different human tumors, the IGF2 Loss of Imprinting (LOI) results in IGF-2- and IGF2-derived intronic miR-483 overexpression. Based on these activities, the purpose of this study was to investigate the overexpression of IGF-2, IGF-1R, and miR-483. Using an immunohistochemical approach, we demonstrated an intense colocalized epithelial overexpression of IGF-2 and IGF-1R in most pterygium samples (Fisher's exact test, p = 0.021). RT-qPCR gene expression analysis confirmed IGF2 upregulation and demonstrated miR-483 expression in pterygium compared to normal conjunctiva (253.2-fold and 12.47-fold, respectively). Therefore, IGF-2/IGF-1R co-expression could suggest their interplay through the two different paracrine/autocrine IGF-2 routes for signaling transfer, which would activate the PI3K/AKT signaling pathway. In this scenario, miR-483 gene family transcription might synergically reinforce IGF-2 oncogenic function through its boosting pro-proliferative and antiapoptotic activity.

Resveratrol inhibits TGF-ß1-induced fibrotic effects in human pterygium fibroblasts.

BACKGROUND: Resveratrol is a polyphenolic phytoalexin which has the properties of anti-oxidant, anti-inflammatory and anti-fibrotic effects. The aim of this study was to investigate the anti-fibrotic effects of resveratrol in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms. METHOD: Profibrotic activation was induced by transforming growth factor-beta1 (TGF-ß1). The expression of profibrotic markers, including type 1 collagen (COL1), α-smooth muscle actin (α-SMA), and fibronectin, were detected by western blot and quantitative real-time-PCR after treatment with various concentrations of resveratrol in HPFs to investigate the anti-fibrotic effects. Relative signaling pathways downstream of TGF-ß1 were detected by Western blot to assess the underlying mechanism. Cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry to evaluate proliferation and drug-induced cytotoxicity. Cell migration and contractile phenotype were detected through wound healing assay and collagen gel contraction assay. RESULTS: The expression of α-SMA, FN and COL1 induced by TGF-ß1 were suppressed by treatment with resveratrol in dose-dependent manner. The Smad3, mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) pathways were activated by TGF-ß1, while resveratrol attenuated those pathways. Resveratrol also inhibited cellular proliferation, migration and contractile phenotype, and induced apoptosis in HPFs. CONCLUSIONS: Resveratrol inhibit TGF-ß1-induced myofibroblast activation and extra cellular matrix synthesis in HPFs, at least partly, by regulating the TGF-ß/Smad3, p38 MAPK and PI3K/AKT pathways.

The role of HPV in the etiopathogenesis of pterygium and the relationship with recurrence.

PURPOSE: The primary aim of this study was to determine the prevalence of HPV in pterygium with polymerase chain reaction (PCR) testing and to investigate the relationship with clinicopathological factors. A secondary aim was to evaluate the relationship between HPV and the recurrence of pterygium. METHODS: The study included 60 patients. PCR analysis was used to determine the presence of HPV. All the patients were followed up in respect of the development of recurrence. Analyses were performed of patient age, pterygium site, specimen and pterygium size, histopathological findings, HPV status, operation technique and postoperative follow-up findings. In the HPV-positive patients, the relationship between HPV subtypes and other factors was evaluated. To determine the risk factors affecting recurrence rates, multivariate Cox regression analysis was applied subsequent to univariate analysis. In the Cox regression model, HPV status, age, sex, specimen size, size and site of pterygium were included among factors that may affect recurrences rates. RESULTS: Of the total 60 patients, the HPV-PCR test result could not be analysed in 14 because of an insufficient sample. Of the 46 patients with sufficient material for HPV-PCR analysis, the HPV-PCR result was positive in 15 (32.6%). The HPV subtype most often determined was type 16. No statistically significant relationship was determined between HPV positivity and HPV subtype and age or sex. Recurrence was determined in 10% of all the patients. Of the cases determined with recurrence, 66.7% were HPV positive. According to Kaplan-Meier analysis, the recurrence rates in HPV-positive and HPV-negative patients were 26.7% and 6.5%, respectively. A statistically significant difference was found between two groups in terms of recurrence rates (p: 0.046). According to the results of multivariate Cox regression analysis, though not statistically significant, the risk of recurrence was increased 6.18 times in HPV-positive patients with pterygium compared to HPV-negative ones. CONCLUSION: HPV infection may have a role in the development of pterygium and recurrence, but may not be sufficient alone. HPV probably has a role in the development of pterygium by acting together with several co-factors in the multi-stage process.