Correlation of Visual Acuity and Outer Retinal Thickness in Myopic Atrophic Maculopathy: A Retrospective Review.

INTRODUCTION: Myopic atrophic maculopathy is prevalent among patients with pathologic myopia and frequently leads to relentless vision loss. Several grading systems were established to facilitate the understanding of myopic atrophic maculopathy. However, the anatomical details in different stages of myopic maculopathy are so far not clearly elucidated. This study aims to investigate the visual acuity and retinal sublayer features in highly myopic eyes with varying severities of myopic atrophic maculopathy (MAM). METHODS: The clinical records of 111 consecutive patients (158 eyes) with high myopia (refractive error ≤ -6.0 D and axial length ≥ 26.0 mm) were reviewed. Fundus photography, optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) were measured. MAM was graded according to the META-analysis for Pathologic Myopia (META-PM) classification system. Myopic choroidal neovascularization (mCNV) and dome-shaped macula (DSM) were also investigated. RESULTS: Among the 158 eyes, 18 (11%), 21(13%), 24 (15%), 25 (16%), 23 (15%), and 24 (15%) had tessellated fundus, diffuse chorioretinal atrophy, diffuse chorioretinal atrophy with DSM, patchy atrophy, patchy atrophy with DSM, and MAM with mCNV, respectively. A total of 23 (15%) eyes had macular atrophy without mCNV. Progressive thinning in the Henle's fiber and outer nuclear layers, myoid and ellipsoid zone (MEZ), outer segment (OS), and interdigitation zone and retinal pigmented epithelium based on the severity of MAM (p-value < 0.001) was found. MEZ and OS were most significantly reduced in thickness (p-value < 0.001). The presence of mCNV demonstrated significant outer retinal layer thinning compared with that of the tessellated fundus (p-value = 0.031). Patchy atrophy with DSM showed statistically poorer BCVA compared with that without (p-value = 0.008). CONCLUSION: Visual acuity and outer retinal sublayer characteristics were correlated with the severity of MAM. Outer retinal sublayer analysis by spectrum-domain OCT shed some light on the mechanisms of MAM progression.

Comparison of Refractive Outcomes in Patients with Highly Myopic Versus Non-highly Myopic Eyes Undergoing Phacovitrectomy.

INTRODUCTION: Combined phacovitrectomy is gaining popularity due to efficiency and immediate visual improvement. However, concerns regarding erroneous intraocular lens (IOL) calculation in combination surgery are increasing, such as myopic shift owing to a thick macula and consequent underestimation of the axial length. Therefore, this study aimed to compare the refractive outcomes of combined phacovitrectomy in patients with highly myopic and non-highly myopic eyes. METHODS: A retrospective chart review was performed on patients who received combined phacoemulsification, intraocular lens implantation, and small gauge pars plana vitrectomy for cataract and macular pathologies in highly myopic and non-highly myopic eyes. Pre- and postoperative evaluation and ocular parameters were recorded, and analyses were performed using the Student's t test and regression analysis. RESULTS: A total of 133 patients with macular pathologies, including myopic tractional maculopathy, macular hole, and epiretinal membrane, were enrolled. SRK II or SRK/T models were used for calculating IOL. The mean absolute error of refraction change was 0.65 D; 83.5% of patients were within 1-D error, 57.9% within 0.5-D error, and 35.3% within 0.25-D error, with SRK/T showing better precision and yielding more myopic shift. Furthermore, the predictive accuracy of SRK II or SRK/T was better in patients with non-highly myopic eyes. Moreover, Barrett's universal II formula was not superior to SRK II or SRK/T in the prediction of postoperative refractive error (p = 0.48). CONCLUSION: Refractive outcomes were satisfactory in the cohort of patients with highly myopic eyes. The combined implementation of SRK II and SRK/T was not inferior to Barrett's universal II formula in predicting satisfactory refractive outcomes. Combination surgery can be an option for patients with both cataract and macular pathologies.

Characteristics and treatment response of polypoidal choroidal vasculopathy in highly myopic eyes.

BACKGROUND: To compare the characteristics and treatment responses of polypoidal choroidal vasculopathy (PCV) between highly myopic and non-highly myopic eyes. METHODS: This retrospective cohort study included patients diagnosed with PCV at the clinic of National Taiwan University Hospital between 2013 and 2019. The diseased eyes were grouped per refractive error and axial length at diagnosis. Imaging data were used to retrieve the PCV characteristics, and electronic medical records were used to retrieve the treatment responses. RESULTS: Among 116 eyes with PCV, 11 eyes of 10 patients were highly myopic; seven of these patients were women. All highly myopic eyes showed a thin subfoveal choroid, while three eyes had a pachychoroid phenotype with significant focal choroidal thickening. After treatment with either intravitreal anti-vascular endothelial growth factor (VEGF) injections, photodynamic therapy (PDT), or both, best-corrected visual acuity was better in the high-myopia group at 1 year. Visual acuity at presentation and the presence of feeder vessels were found to be predictors of the visual outcome. CONCLUSIONS: In this study we reported, to the best of our knowledge, the largest cohort of PCV in highly myopic eyes to date. Female predominance, lower incidence of subretinal haemorrhage, and a thin choroid with a focal pachychoroid phenotype were found to characterise PCV in highly myopic eyes. Visual acuity transiently improved after either anti-VEGF monotherapy or combination therapy with PDT.

Clinical Characteristics of Highly Myopic Patients With Asymmetric Myopic Atrophic Maculopathy-Analysis Using Multimodal Imaging.

Purpose: To evaluate the factors associated with asymmetric myopic atrophic maculopathy (MAM) in highly myopic patients. Methods: We enrolled highly myopic patients with asymmetric MAM according to the atrophy, traction, and neovascularization (ATN) classification. The results of color fundus photography, optical coherence tomography (OCT), OCT angiography, and corneal visualization Scheimpflug technology (Corvis ST tonometry) were reviewed. The association between inter-eye differences in clinical features and MAM grading was analyzed using logistic regression analysis. Results: Among the 72 eyes of 36 patients 61.0 ± 9.3 years of age, 9, 33, 17, and 13 eyes had A1, A2, A3, and A4, respectively. The mean axial length was 30.44 ± 1.92 mm, and there was no significant difference between eyes with less severe and more severe MAM. The inter-eye differences in MAM grading were associated with the inter-eye differences in the presence of Bruch's membrane defects (P = 0.014), ellipsoid zone disruption (P = 0.013), vessel density of the deep retinal layer (P = 0.022), foveal avascular zone circularity (P = 0.012), foveal avascular zone area (P = 0.049), flow area of the choriocapillaris (P = 0.013), vessel diameter (P = 0.045), and fractal dimension (P = 0.015). No Corvis ST parameter was statistically significant. A higher difference in the choriocapillaris flow area (P = 0.013; adjusted odds ratio = 1.10 [1.02-1.18]) remained associated with higher inter-eye differences in MAM grading in the multivariable regression. Conclusions: A smaller choriocapillaris flow area was associated with more severe MAM, suggesting that vascular factors play pivotal roles in MAM.

Biomarkers in the pathogenesis of epiretinal membrane and myopic traction maculopathy: Effects of internal limiting membrane incompliance and posterior staphyloma.

BACKGROUND: This study compared the structural and vascular intraretinal changes between epiretinal membrane and myopic traction maculopathy eyes. METHODS: An observational retrospective study of treatment-naïve epiretinal membrane and myopic traction maculopathy eyes was conducted to identify biomarkers of a 3 × 3 mm macular region centered on the fovea, using optical coherence tomography angiography. RESULTS: The myopic traction maculopathy and epiretinal membrane groups comprised 27 and 32 eyes, respectively. In the myopic traction maculopathy group, the spherical equivalent was more myopic and the axial length was longer than in the epiretinal membrane group. Myopic traction maculopathy eyes had larger outer and smaller inner retinal volumes, larger area and perimeter of foveal avascular zones, greater circularity of foveal avascular zones, and smaller foveal vessel density in the superficial layer than epiretinal membrane eyes. Internal limiting membrane incompliance and staphyloma were significantly more in the myopic traction maculopathy group than in the epiretinal membrane group. CONCLUSIONS: The intraretinal changes in myopic traction maculopathy eyes compared with epiretinal membrane eyes showed larger avascular zones, which may have been caused by tangential internal limiting membrane incompliance. Anteroposterior traction forces from staphyloma in myopic traction maculopathy eyes may lead to larger outer retinal volumes. In epiretinal membrane eyes, traction forces confined to the superficial retina caused large inner retinal volumes and foveal acircularity.

Natural course of the intraretinal hyperreflective sign after macular haemorrhage absorption in eyes with pathologic myopia.

PURPOSE: We investigated the natural course of the intraretinal hyperreflective (IRH) sign after macular haemorrhage (MHE) absorption in eyes with pathologic myopia. METHODS: This prospective observational cohort study evaluated 28 patients with pathologic myopia and MHE. The eyes were categorized into IRH and non-IRH sign groups according to IRH sign development. All eyes were evaluated; follow-up visits were scheduled at 1, 3, 6, 12 and 24 months after MHE absorption. RESULTS: Of 28 patients (14 eyes each in the IRH and non-IRH groups), nine (32.1%) were men and 19 (67.9%) were women. The average age (mean ± SD) was 46.64 ± 11.92 versus 52.71 ± 12.19 years in the IRH and non-IRH groups. The IRH sign coincided with the MHE invasion site. The sign persisted for the entire follow-up period in all but two eyes, in which it disappeared at 12 and 24 months, respectively. Maximal MHE thickness was significantly greater in the IRH sign group (162.9 ± 67.84 versus 104.2 ± 32.34 µm, p = 0.013). The mean logarithm of the minimum angle of resolution visual acuity was significantly better in the non-IRH sign group at 12 (p = 0.029) and 24 (p = 0.033) months. The incidence of myopic traction maculopathies (MTM) was significantly higher in the IRH (57.1%) than in the non-IRH sign group (14.3%; p = 0.046). CONCLUSION: The IRH sign can develop after MHE in pathologic myopia and can remain stable long after MHE absorption; furthermore, it is predictive of future MTM.

Reconstructing Foveola by Foveolar Internal Limiting Membrane Non-Peeling and Tissue Repositioning for Lamellar Hole-Related Epiretinal Proliferation.

Differences in the pathogenesis and clinical characteristics between lamellar macular hole (LMH) with and without LMH-associated epiretinal proliferation (LHEP) can have surgical implications. This study investigated the effects of treating LHEP by foveolar internal limiting membrane (ILM) non-peeling and epiretinal proliferative (EP) tissue repositioning on visual acuity and foveolar architecture. Consecutive patients with LHEP treated at our institution were enrolled. The eyes were divided into a conventional total ILM peeling group (group 1, n = 11) and a foveolar ILM non-peeling group (group 2, n = 22). In group 2, a doughnut-shaped ILM was peeled, leaving a 400-µm-diameter ILM without elevated margin over the foveola after EP tissue repositioning. The EP tissue was elevated, trimmed, and inverted into the LMH. Postoperatively, the LMH was sealed in all eyes in group 2, with significantly better best-corrected visual acuity (-0.26 vs -0.10 logMAR; p = 0.002). A smaller retinal defect (p = 0.003), a more restored ellipsoid zone (p = 0.002), and a more smooth foveal depression (p < 0.001) were achieved in group 2. Foveolar ILM non-peeling and EP tissue repositioning sealed the LMH, released the tangential traction, and achieved better visual acuity. The presumed foveolar architecture may be reconstructed surgically. LMH with LHEP could have a combined degenerative and tractional mechanism.

Myopic traction maculopathy biomarkers on optical coherence tomography angiography-An overlooked mechanism of visual acuity correction in myopic eyes.

BACKGROUND/OBJECTIVES: Myopic traction maculopathy of the retinoschisis type is a unique entity that has been frequently overlooked in refraction correction in daily practice in myopic eyes. The objective of this study was to describe the imaging characteristics of myopic traction maculopathy (MTM) seen on optical coherence tomography angiography (OCTA) and to detect biomarkers of the associated functional changes. SUBJECTS/METHODS: We performed OCTA on eyes with MTM and retinoschisis (RS group; n = 27) and highly myopic eyes without MTM (control group; n = 27). The RS group was further divided into a dome-shaped macula (DSM) group and a non-DSM group. The groups were compared for morphologic and perfusion characteristics. RESULTS: The RS and control groups had comparable spherical equivalence (p = 0.65), but the RS group had worse best-corrected visual acuity (p < 0.01), larger retinal volumes (p < 0.01), and greater subfoveal choroid capillary vessel density values (p = 0.04). Compared to the non-DSM group, the DSM group had significantly smaller inner retinal volumes (p = 0.05) and significantly larger choroid capillary vessel density values in both the whole macula (p = 0.005) and the fovea (p = 0.03). CONCLUSIONS: Our high-resolution OCTA morphologic and vascular perfusion data correlated well with functional abnormalities encountered in myopic eyes. Changes in vessel density may elucidate the pathogenesis of MTM and characterize the mechanical stretch forces acting in eyes with MTM.

Spectral-domain optical coherence tomography of peripheral lattice degeneration of myopic eyes before and after laser photocoagulation.

PURPOSE: To investigate the microstructural characteristics of lattice degenerations before and after laser photocoagulation in myopic eyes by spectral-domain optical coherence tomography (SD-OCT). METHODS: Twenty-five eyes of 25 consecutive patients at the High Myopia Clinic of the National Taiwan University Hospital were retrospectively reviewed. Myopic eyes with peripheral lattice degeneration were enrolled in the study. Best-corrected visual acuity (BCVA), axial length measurement, color fundus photography was performed. SD-OCT analyses on the lattice degeneration were performed before and after prophylactic laser photocoagulation. All patients were followed for at least 6 months. RESULTS: In total, 25 myopic eyes with peripheral lattice degenerations were studied. The mean refractive error was -9.92 ± 4.77 Diopters (D) with 21 (84%) of the eye being highly myopic (Over -6.0 D). The average axial length was 27.7 ± 1.86 mm. In these myopic eyes, retinal thinning was the most common finding (92%), followed by vitreoretinal traction (72%), retinoschisis (44%), vitreous membrane with deposits (36%), and retinal break with subretinal fluid (4%). A blunting effect of the vitreoretinal tractions was found after laser photocoagulation. CONCLUSION: To our knowledge we firstly investigated the pre- and post-laser photocoagulation microstructural changes using SD-OCT. It demonstrated a beneficial effect of retinoplasty, which released vitreoretinal tractions after laser photocoagulation. Combined with the findings of subtle microstructural retinal breaks and subretinal fluid, early prophylactic laser treatment warrants sincere consideration in these myopic eyes.

Multimodal imaging of linear lesions in the fundus of pathologic myopic eyes with macular lesions.

PURPOSE: To detect, using multimodal imaging, lacquer cracks (LCs) and myopic stretch lines (MSLs) in pathologic myopic eyes with macular hemorrhage (MHE) and those without. METHODS: We collected 18 consecutive pathologic myopic eyes (spherical equivalent ≤ -8.0 diopters) that had presented with linear, yellowish-white lesions in the macula. We categorized the eyes into either the MHE group or the non-MHE group. All underwent fluorescein angiography (FA), near infrared autofluorescence (NIA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT). RESULTS: In all 18 eyes, the linear lesions were hyperfluorescent under NIA imaging, but hypofluorescent under ICGA. All ten eyes in the MHE group had LCs, and two had both LCs and MSLs. None of the eight eyes in the non-MHE group had LCs. Regarding proximity to the MHE, LCs tended to locate closer than MSLs. Incidental perforating scleral vessels were clearly visible on the tracked SD-OCT scanning line, joining the choroid beneath the border of MHE. Sample cases are illustrated using delicate photographs and explanations. CONCLUSION: NIA imaging combined with SD-OCT and ICGA can detect and differentiate early the subtle difference between the two types of linear lesions in pathological myopic eyes. Notably, MSLs were not associated with MHEs or LCs in our consecutive series.

Vitrectomy with a modified temporal inverted limiting membrane flap to reconstruct the foveolar architecture for macular hole retinal detachment in highly myopic eyes.

PURPOSE: We investigated the surgical results of macular hole retinal detachment (MHRD) with a modified C-shaped temporal inverted internal limiting membrane (ILM) flap to reconstruct the foveolar architecture in highly myopic eyes. METHODS: Eighteen highly myopic eyes with MHRD in 17 patients who underwent a vitrectomy with a modified C-shaped temporal inverted ILM flap were followed for 12 months. Anatomic outcomes were evaluated by fundus examinations and optical coherence tomography. The preoperative and postoperative best-corrected visual acuities (BCVAs) were compared as functional outcomes. RESULTS: Women accounted for 88% of the MHRD patients. The mean age was 60.2 ± 8.2 years. The mean axial length was 29.25 ± 2.10 mm. Type 1 and type 2 MHRD was present in four eyes and 14 eyes, respectively. After a single surgery, the hole was closed in 18 eyes (100%). Retinal attachment was achieved in 95%. Persistent shallow subretinal fluid (SRF) was noted in one case, which was resolved at follow-up. The surgery significantly improved BCVAs (from 1.7 ± 0.6 to 0.72 ± 0.4 logarithm of the minimum angle of resolution units [p < 0.001]) at the last visit. In total, 94.4% of the eyes had restored foveolar architecture. Ellipsoid zone recovery within the foveola was found in 77.8% of the eyes. CONCLUSION: A vitrectomy and modified C-shaped inverted temporal ILM flap is effective for closing MHs, reattaching the retina, restoring the foveolar architecture and significantly improving the postoperative BCVA in MHRD patients. This technique is feasible, and we propose 'presumed' Müller cell cone repair in MHRD surgery.

History and development of ophthalmology in Taiwan.

Western medicine was first introduced to Taiwan by medical missionaries in the mid-19th century. Modernization of medicine was systematically transplanted to Taiwan in the Japanese colonial period, and ophthalmology was established third among hospital departments, following internal medicine and surgery. Dr Hidetaka Yamaguchi, an ophthalmologist, was the first head of the Taihoku Hospital, later known as National Taiwan University Hospital (NTUH; Taipei, Taiwan). Ophthalmologists during the colonial period conducted studies on tropical and infectious eye diseases. After World War II, ophthalmologists at NTUH played an important role in medical education, residency training, studies, and teaching. Dr Yan-Fei Yang established the Taiwan Ophthalmological Society in 1960 and instituted its official journal in 1962. Dr Ho-Ming Lin established the Department of Ophthalmology at the Tri-Service General Hospital in the 1950s and the Veterans General Hospital in the 1960s. Taiwan ophthalmologists eradicated trachoma by 1971. Cataract surgery and penetrating keratoplasty were initially performed in the 1960s. Currently, there are about 1600 ophthalmologists in Taiwan conducting an estimated 120,000 cataract surgeries and 600 corneal transplantations annually. Many subspecialty societies have been established recently that serve to educate Taiwanese ophthalmologists and to connect with international ophthalmic societies. Taiwan ophthalmologists continue to contribute to the advancement of ophthalmic knowledge globally.

Macular retinal detachment associated with intrachoroidal cavitation in myopic patients.

PURPOSE: To investigate the clinical characteristics and treatment outcomes of macular retinal detachment (MRD) associated with intrachoroidal cavitation (ICC) in myopic patients. METHODS: In this retrospective, consecutive, interventional case series, five patients with ICC and associated MRD were enrolled from January 2005 to December 2012. Basic ocular characteristics and clinical appearances of their ICC and MRD were recorded. Individual treatment courses were assessed with fundus photographs and serial optical coherence tomography. RESULTS: The average age and refraction were 43.8 ± 11.0 years old and -9.37 ± 2.73 diopters, respectively. Initial BCVA ranged from 20/100 to 20/30. Definite communication between the ICC and the subretinal space was noted in one case, suspected curvilinear communication in two cases, and between the peripapillary area and the subretinal space in two cases. Two cases received intravitreal injection of perfluoropropane and peripapillary laser; subretinal fluid (SRF) resolved in one and decreased in the other. One case had SRF reabsorbed after prolonged use of topical carbonic anhydrase inhibitor. CONCLUSIONS: ICC in high myopic patients may be associated with MRD. There might be communication between the ICC and the subretinal space. Intravitreal injection of an expansile gas may be beneficial, but the best treatment remains undetermined.

Focal foveal atrophy of unknown etiology: clinical pictures and possible underlying causes.

BACKGROUND/PURPOSE: Focal foveal atrophy is defined as the presence of a small, focal, ill-defined, hypopigmented foveal or juxtafoveal lesion, with the remaining retina unaffected. The purpose of this study was to report the clinical characteristics and optical coherence tomography (OCT) in patients with focal foveal atrophy of unknown etiology. METHODS: The study was a retrospective observational case series. Data collected included complete ocular examination results for best corrected visual acuity (BCVA), ophthalmoscopy, fundus photography, fluorescein angiography, color sense discrimination tests, visual field tests, and OCT examinations. RESULTS: Twenty-three eyes in 21 patients were examined. The mean patient age was 49.2 ± 15.4 years. The mean BCVA was 20/25. The 21 patients were divided into three groups according to OCT results. Group 1 eyes (n = 10) had intact inner and outer hyperreflective layers (HRLs), with the signal of the inner HRL corresponding to the junction between the inner and outer photoreceptor segments and the outer HRL corresponding to the retinal pigment epithelium (RPE). Group 2 eyes (n = 9) had small hyporeflective defects with defects in the inner HRL at the fovea but an intact outer HRL. Group 3 eyes (n = 4) had small hyporeflective defects in both the inner and outer HRLs at the fovea. Groups 3 eyes had significantly lower visual acuity compared to Group 1 eyes and Group 2 eyes. There was no significant difference in visual acuity between Group 1 and Group 2 eyes. There were no significant differences among the groups with respect to color vision or foveal thickness. CONCLUSION: This is the first report of clinical presentations for patients with focal foveal atrophy of unknown etiology. OCT aided in the diagnosis and assessment of the degree of retinal structural abnormalities, but the real etiology of foveal atrophy remains unclear.

Long-term outcome of foveolar internal limiting membrane nonpeeling for myopic traction maculopathy.

PURPOSE: To investigate the long-term results of a novel technique to preserve the foveolar cone without peeling off the foveolar internal limiting membrane (ILM) during myopic traction maculopathy surgery. METHODS: Nineteen patients (19 eyes) were retrospectively studied and divided into 2 groups by the extent of ILM peeled and followed for more than 3 years. Group 1: foveolar ILM nonpeeling group (FN) (12 eyes) and Group 2: total peeling of foveal ILM group (TP) (7 eyes). A donut-shaped ILM was peeled off, leaving a 400-µm diameter ILM over foveola with a sharp margin in FN group. RESULTS: Macular hole was developed in 2 of the 7 eyes (28.6%) in the TP group and none in the FN group. Long-term central fovea thickness thinning and decrease of vision were found in the TP group, but not in the FN group (P < 0.05). Inner segment/outer segment line recovered in 75% of the 12 eyes in the FN group, but in only 14.3% of the 7 eyes in the TP group. CONCLUSION: Preservation of the foveolar cone by foveola nonpeeling surgery correlates with better anatomical and visual results than total peel, prevents long-term foveolar retinal thinning, and successfully saves the fovea from macular hole formation.

Foveola nonpeeling internal limiting membrane surgery to prevent inner retinal damages in early stage 2 idiopathic macula hole.

PURPOSE: The purpose of this study was to investigate and present the results of a new vitrectomy technique to preserve the foveolar internal limiting membrane (ILM) during ILM peeling in early stage 2 macular holes (MH). METHODS: The medical records of 28 consecutive patients (28 eyes) with early stage 2 MH were retrospectively reviewed and randomly divided into two groups by the extent of ILM peeing. Group 1: foveolar ILM nonpeeling group (14 eyes), and group 2: total peeling of foveal ILM group (14 eyes). A donut-shaped ILM was peeled off, leaving a 400-µm-diameter ILM over foveola in group 1. RESULTS: Smooth and symmetric umbo foveolar contour was restored without inner retinal dimpling in all eyes in group 1, but not in group 2. The final vision was better in group 1 (P = 0.011). All eyes in group 1 (100 %) and seven of 14 eyes in group 2 (50 %)regained the inner segment/outer segment (IS/OS) line. Restoration of the umbo light reflex was found in 12 of 14 eyes in group 1 (86 %) but none in group 2 (0 %). CONCLUSIONS: Nonpeeling of the foveolar ILM in early stage 2 idiopathic MH surgery prevented inner retinal damages, restored umbo light reflex, achieved better foveolar microstructures, and led to better final visual acuity.

Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin ανß3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells.

Diabetes causes a number of metabolic and physiological abnormalities in the retina. Many of the molecular and physiological abnormalities that develop during diabetic retinopathy are due to inflammation. Monocyte chemoattractant protein-1 (MCP-1) is an important factor involved in diabetic retinopathy. In a previous study, we found that cysteine-rich 61 (Cyr61), an important angiogenic factor, also plays an important role in diabetic retinopathy. In addition to the direct effects of Cyr61, we observed that Cyr61 can induce the expression of MCP-1. However, the mechanism through which this occurs is not completely understood in chorioretinal vascular endothelial cells. We therefore investigated the effects of Cyr61 on MCP-1 expression in this cell type. Cyr61 stimulated the expression of MCP-1 at the mRNA, protein, and secreted protein levels in a dose-dependent and time-dependent manner. Both total MCP-1 levels and secreted MCP-1 levels were attenuated during the response to Cyr61 stimulation by pretreatment with integrin ανß3-blocking antibodies, a FAK inhibitor (PF573228), a PI3K inhibitor (LY294002), and an Akt inhibitor (A6730). Electrophoretic mobility shift assays revealed that the above inhibitors suppressed the activation of NF-κB. Additionally, deletion of the NF-κB-binding element in the MCP-1 gene promoter led to a decrease in expression in luciferase reporter assays. These results show that the induction of MCP-1 by Cyr61 is mediated through the activation of the integrin ανß3, FAK, PI3K/Akt, and IKK/NF-κB pathways in chorioretinal vascular endothelial cells.

Chitosan oligosaccharides attenuates oxidative-stress related retinal degeneration in rats.

This study investigated the therapeutic potential and mechanisms of chitosan oligosaccharides (COS) for oxidative stress-induced retinal diseases. Retinal oxidative damage was induced in Sprague-Dawley rats by intravitreal injection of paraquat (PQ). Low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS was intragastrically given for 14 days after PQ injection. Electroretinograms were performed to determine the functionality of the retinas. The surviving neurons in the retinal ganglion cell layer and retinal apoptosis were determined by counting Neu N-positive cells in whole-mounted retinas and TUNEL staining, respectively. The generation of reactive oxygen species (ROS) was determined by lucigenin- and luminol-enhanced chemiluminescence. Retinal oxidative damages were assessed by staining with nitrotyrosine, acrolein, and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical studies were used to demonstrate the expression of nuclear factor-kappa B (NF-κB) p65 in retinas. An in vitro study using RGC-5 cells was performed to verify the results. We demonstrated COS significantly enhanced the recovery of retinal function, preserved inner retinal thickness, and decreased retinal neurons loss in a dose-dependent manner. COS administration demonstrated anti-oxidative effects by reducing luminol- and lucigenin-dependent chemiluminenscense levels and activating superoxide dismutase and catalase, leading to decreased retinal apoptosis. COS markedly reduced retinal NF-κB p65. An in vitro study demonstrated COS increased IκB expression, attenuated the increase of p65 and thus decreased NF-κB/DNA binding activity in PQ-stimulated RGC-5 cells. In conclusion, COS attenuates oxidative stress-induced retinal damages, probably by decreasing free radicals, maintaining the activities of anti-oxidative enzymes, and inhibiting the activation of NF-κB.

Transplantation of induced pluripotent stem cells without C-Myc attenuates retinal ischemia and reperfusion injury in rats.

Induced pluripotent stem cells (iPSC) are novel stem cell populations, but the role of iPSC in retinal ischemia and reperfusion (I/R) injury remains unknown. Since oncogene c-Myc is substantially contributed to tumor formation, in this study, we investigated the effects, mechanisms and safety of subretinal transplantation of iPSC without c-Myc (non-c-Myc iPSC) in a rat model of retinal I/R injury. Retinal I/R injury was induced by raising the intraocular pressure of Sprague-Dawley rats to 110 mmHg for 60 min. A subretinal injection of non-c-Myc iPSC or murine epidermal fibroblast was given 2 h after I/R injury. Electroretinograms (ERG) were performed to determine the functionality of the retinas. The surviving retinal ganglion cells (RGCs) and retinal apoptosis following I/R injury were determined by counting NeuN-positive cells in whole-mounted retinas and TUNEL staining, respectively. The generation of reactive oxygen species (ROS) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the retinal tissues were determined by lucigenin- and luminol-enhanced chemiluminescence and enzyme-linked immunosorbent assay (ELISA). The degree of retinal oxidative damage was assessed by nitrotyrosine, acrolein, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining. The expression of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF) in retinas was measured by immunohistochemistry and ELISA. We found that subretinal transplantation of non-c-Myc iPSC significantly suppressed the I/R-induced reduction in the ERG a- and b-wave ratio, attenuated I/R-induced loss of RGCs and remarkably ameliorated retinal morphological changes. Non-c-Myc iPSC potentially increased the activities of SOD and CAT, decreased the levels of ROS, which may account for preventing retinal cells from apoptotic cell death. In addition, the levels of BDNF and CNTF in retina were significantly elevated in non-c-Myc iPSC-treated eyes. Track the non-c-Myc iPSC after transplantation, most transplanted cells are remained in the subretinal space, with spare cells express neurofilament M markers at day 28. Six months after transplantation in I/R injured rats, no tumor formation was seen in non-c-Myc iPSC graft. In conclusion, non-c-Myc iPSC effectively rescued I/R-induced retinal damages and diminished tumorigenicity. Non-c-Myc iPSC transplantation attenuated retinal I/R injury, possibly via a mechanism involving the regulation of oxidative parameters and paracrinal secretion of trophic factors.