Properties of fhRPE cells align with a functionally normal RPE in vivo, while ARPE-19 cells resemble a pathologic or aged RPE. These results suggest a utility for both cell types in understanding distinct, particular aspects of RPE function.

This report to our knowledge is the first description of the spatial distribution of A2E in the human RPE by imaging mass spectrometry. These data demonstrate that the accumulation of A2E is not responsible for the increase in lipofuscin fluorescence observed in the central RPE with aging.

Patients with nonexudative ("dry") age-related macular degeneration (AMD) frequently also develop neovascular ("wet") AMD, suggesting a common pathomechanism. Increased vascular endothelial growth factor A (VEGF-A) has been implicated in the pathogenesis of choroidal neovascularization (CNV) in neovascular AMD, while its role in nonexudative AMD that manifests with progressive retinal pigment epithelium (RPE) and photoreceptor degeneration is not well defined. Mice with overall increased VEGF-A levels develop progressive morphological features of both forms of AMD, suggesting that an increase in VEGF-A has a direct age-dependent adverse effect on RPE and photoreceptor function independently of its CNV-promoting proangiogenic effect. Here we provide evidence for this hypothesis and show that morphological RPE abnormalities and retinal thinning in mice with increased VEGF-A levels correlate with progressive age-dependent attenuation of visual function with abnormal electroretinograms and reduced retinal rhodopsin levels. Retinoid profiling revealed a progressive reduction of 11-cis and all-trans retinal in the retinas of these mice, consistent with an impaired retinoid transport between the RPE and photoreceptors. These findings suggest that increased VEGF-A leads to an age-dependent RPE and retinal dysfunction that occurs also at sites where no CNV lesions form. The data support a central role of increased VEGF-A not only in the pathogenesis of neovascular but also of nonexudative AMD.

This study demonstrated that suppressing HDAC2 expression can effectively reduce ischemic retinal injury. Our results support the idea that the development of selective HDAC2 inhibitors may provide an efficacious treatment for ischemic retinal injury.

Purpose: Epiretinal proliferation is a distinct clinical entity from epiretinal membrane that is classically associated with lamellar macular holes, but its prevalence and association with full-thickness macular holes (FTMH) have not been well described. We characterize MHEP macular hole associated epiretinal proliferation (MHEP) and its effects on long-term surgical outcomes. Design: Multi-center, interventional, retrospective case control study. Subjects: Consecutive eyes that underwent surgery for FTMH with a minimum of 12-months follow-up. Methods: All eyes underwent pars plana vitrectomy, removal of any epiretinal membranes, and gas tamponade, with or without internal limiting membrane peeling. Spectral domain optical coherence tomography imaging was obtained pre- and post-operatively. Main Outcome Measures: Improvement in visual acuity and single surgery hole closure rates in eyes with, versus without, MHEP at 12 months. Results: 725 charts were analyzed, and 113 patients met inclusion criteria. Of 113 eyes with FTMH, 30 (26.5%) had MHEP. Patients with FTMH and MHEP were older (P < 0.002), more often male (P = 0.001), and with more advanced macular hole stages than those without MHEP (P = 0.010). A full posterior vitreous detachment was more common in eyes with MHEP (P < 0.004). FTMH with MHEP had significantly less improvement in visual acuity 12-months postoperatively (P = 0.019) with higher rates of ellipsoid and external limiting membrane defects (P < 0.05) and with a higher rate of failure to close with one surgery compared to FTMH without MHEP (26.7% versus 4.8% [P = 0.002]). Peeling the internal limiting membrane was associated with improved rates of hole closure in FTMH with MHEP (P < 0.001). Multivariable testing confirmed that the presence of MHEP was an independent risk factor for less visual improvement (P = 0.031), single-surgery non-closure (P = 0.009), and that ILM peeling improved single-surgery closure rates (P = 0.026). Conclusions: We found that FTMH with MHEP has poorer anatomic and visual outcomes after vitrectomy compared to FTMH without MHEP. ILM peeling was associated with improved closure rates and should be considered when MHEP is detected preoperatively.