This study aimed to investigate whether the transplantation of genetically engineered bone marrow-derived mesenchymal stromal cells (MSCs) to overexpress brain-derived neurotrophic factor (BDNF) could rescue the chronic degenerative process of slow retinal degeneration in the rd6 (retinal degeneration 6) mouse model and sought to identify the potential underlying mechanisms. Rd6 mice were subjected to the intravitreal injection of lentivirally modified MSC-BDNF or unmodified MSC or saline. In vivo morphology, electrophysiological retinal function (ERG), and the expression of apoptosis-related genes, as well as BDNF and its receptor (TrkB), were assessed in retinas collected at 28 days and three months after transplantation. We observed that cells survived for at least three months after transplantation. MSC-BDNF preferentially integrated into the outer retinal layers and considerably rescued damaged retinal cells, as evaluated by ERG and immunofluorescence staining. Additionally, compared with controls, the therapy with MSC-BDNF was associated with the induction of molecular changes related to anti-apoptotic signaling. In conclusion, BDNF overexpression observed in retinas after MSC-BDNF treatment could enhance the neuroprotective properties of transplanted autologous MSCs alone in the chronically degenerated retina. This research provides evidence for the long-term efficacy of genetically-modified MSC and may represent a strategy for treating various forms of degenerative retinopathies in the future.

The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT), electrophysiological function (ERG), and the expression of selected oxidative stress‐, apoptosis‐, and autophagy‐related proteins were assessed in retinas of 12‐month‐old C3‐deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1) alleviation of the age‐dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2) significantly higher levels of antioxidant enzymes (catalase and glutathione reductase) and the antiapoptotic survivin and Mcl‐1/Bak dimer, (3) lower expression of the cellular oxidative stress marker—4HNE—and decreased activity of proapoptotic caspase‐3, (4) ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE) layer, and (5) significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina. Our findings shed light on mechanisms of age‐related retinal alterations by identifying C3 as a potential therapeutic target for retinal aging.

Introduction: The aim of this study was to examine retinal vessels in autosomal dominant polycystic kidney disease (ADPKD) patients with normal kidney function and without diabetes mellitus. Materials and Methods: We enrolled 39 adult individuals with ADPKD and 45 gender- and age-matched individuals as controls. A full ophthalmologic examination, including retinal vessel caliber and reactions to flicker stimulation analysis and grading of hypertensive retinopathy according to the Keith-Wagener classification, was performed. Results: Multivariable analysis of ADPKD patients and controls, adjusted for age, gender, estimated glomerular filtration rate (e-GFR) and the presence of hypertension, revealed that ADPKD was an independent factor associated with lower arteriovenous ratio (AVR) values (by 0.069 on average, β = −0.50, p < 0.0001). The severity of hypertensive retinopathy according to the Keith-Wagener classification appeared to be more advanced in the ADPKD group than in the controls, despite the lack of vascular abnormalities, such as retinal hemorrhages, exudates, cotton wool spots or papilledema, as well as microaneurysms, which are very characteristic signs of ADPKD in other vascular beds. Conclusions: Lower AVR values could be a specific pathophysiological ocular manifestation of systemic vasculopathy in the course of ADPKD.