Upregulation of ASPP2 expression alleviates the development of proliferative vitreoretinopathy in a rat model

AIM: To investigate whether upregulation of apoptosis-stimulating p53 protein 2 (ASPP2) expression could alleviate the development of proliferative vitreoretinopathy (PVR) in a rat model. METHODS: ASPP2-lentivirus or scrambled-lentivirus were transfected into ARPE-19 cells, followed with measurements of cell cytotoxicity by cell counting kit-8 assay. ASPP2 upregulation was confirmed by Western blotting and immunocytochemistry. Then ARPE-19 cells pretreated with ASPP2-lentivirus were intravitreally injected to Brown Norway rats to induce PVR models. PVR development and retinal function were evaluated by retinal photography and electroretinography, respectively. Finally, epithelial-mesenchymal transition as well as autophagy were investigated in rats’ retinas via Western blotting. RESULTS: Protein expression of ASPP2 was significantly upregulated by ASPP2-lentivirus transfection in ARPE-19 cells. The development and progression of PVR were impeded significantly in rats with intravitreal injection of ARPE-19 cells pretreated with ASPP2-lentivirus. Accordingly, retinal functions were less affected and PVR grades were much lower in rats with ASPP2-lentivirus compared to scrambled-lentivirus treatment. Moreover, epithelial-mesenchymal transition and autophagy markers were decreased in the retinas of rats treated with ASPP2-lentivirus. CONCLUSION: ASPP2-lentivirus transfected to ARPE-19 cells mitigates the progression of PVR in rat models, which might be partly through reduced autophagy and attenuated epithelial-mesenchymal transition. ASPP2 might stand as a new approach for PVR treatment in the future.

Oscillatory Potentials in Achromatopsia as a Tool for Understanding Cone Retinal Functions

Achromatopsia (ACHM) is an inherited autosomal recessive disease lacking cone photoreceptors functions. In this study, we characterize the time-frequency representation of the full-field electroretinogram (ffERG) component oscillatory potentials (OPs), to investigate the connections between photoreceptors and the inner retinal network using ACHM as a model. Time-frequency characterization of OPs was extracted from 52 controls and 41 achromat individuals. The stimulation via ffERG was delivered under dark-adaptation (DA, 3.0 and 10.0 cd·s·m−2) to assess mixed rod-cone responses. The ffERG signal was subsequently analyzed using a continuous complex Morlet transform. Time-frequency maps of both DA conditions show the characterization of OPs, disclosing in both groups two distinct time-frequency windows (~70–100 Hz and >100 Hz) within 50 ms. Our main result indicates a significant cluster (p < 0.05) in both conditions of reduced relative power (dB) in ACHM people compared to controls, mainly at the time-frequency window >100 Hz. These results suggest that the strongly reduced but not absent activity of OPs above 100 Hz is mostly driven by cones and only in small part by rods. Thus, the lack of cone modulation of OPs gives important insights into interactions between photoreceptors and the inner retinal network and can be used as a biomarker for monitoring cone connection to the inner retina.

Electroretinogram responses in myopia: a review

The stretching of a myopic eye is associated with several structural and functional changes in the retina and posterior segment of the eye. Recent research highlights the role of retinal signaling in ocular growth. Evidence from studies conducted on animal models and humans suggests that visual mechanisms regulating refractive development are primarily localized at the retina and that the visual signals from the retinal periphery are also critical for visually guided eye growth. Therefore, it is important to study the structural and functional changes in the retina in relation to refractive errors. This review will specifically focus on electroretinogram (ERG) changes in myopia and their implications in understanding the nature of retinal functioning in myopic eyes. Based on the available literature, we will discuss the fundamentals of retinal neurophysiology in the regulation of vision-dependent ocular growth, findings from various studies that investigated global and localized retinal functions in myopia using various types of ERGs.

Electrophysiological assessment of retinal functions by ERG in Ischemia/Reperfusion (I/R) Allium cepa pre-treated mice

Retinal disorders are the one of the most challenging and complex degenerative diseases that need to be addressed because of rapid increase in the number of affected individuals. Most of the available treatments strategies are inadequate to exert permanent solution to the patients. Therefore, as an alternative approach we wanted to test the efficacy of Allium cepa(A. cepa) in an Ischemia/Reperfusion (I/R) mouse model. We orally administered the aqueous extract of A. cepa at different dosages 100 mg/kg, 200 mg/kg, 300 mg/kg 24 hrs prior to the surgery. Electroretinogram (ERG) analysis was carried out at 7 day, 21 day, and 28 day after the surgery. ERG recording depicted that A. cepa administration is able to increase the implicit time but not at the statistically significant level for which larger sample size and deeper analysis is required.

Vision Dysfunction in Circadian Clock Gene Bmal Mice

Background and Hypothesis: The circadian rhythm disruption due to shift work results in a range of disorders such as metabolic disturbances, obesity, cardiovascular diseases, and insulin resistance. Interestingly, the core clock gene Brain and Muscle ARNT-Like 1 (Bmal1), is dysfunctional in shift workers. We reasoned dysfunctional Bmal will affect normal vision function. To do so, a genetically modified mouse with disrupted Bmal was assessed for visual function. We hypothesized that Bmal knockout mice will exhibit reduced retinal functions such as impaired acuity, accommodation, and tracking. Experimental Design or Project Methods: The Bmal+/- mice were inbred and genotyped to obtain wild-types (WT), Bmal+/-, and Bmal-/-. To assess the retinal function, we performed electroretinogram (ERG) recordings at the zeitgeber times (ZT) of 0, 6, 12, and 18 which correspond to 7 AM, 1 PM, 7 PM, and 1 AM, respectively, under both scotopic and photopic conditions. The optokinetic response (OKR) assessments were measured in between ZT-3-ZT7. Results: Consistent with previous studies, the ‘a’ wave and ‘b’ wave amplitudes of WT mice demonstrated a circadian rhythm under scotopic condition. There was a decrease in ERG amplitude of Bmal+/-, and Bmal-/- when compared to the WT group. Under photopic conditions, the circadian peak of ERG amplitude was reversed for Bmal-/- when compared to both WT and Bmal+/- mice. The OKR assessment was decreased substantially for Bmal+/- (0.3748c/d), and Bmal-/- (0.3130c/d) as compared to the WT mice (0.4827c/d). Conclusion and Potential Impact: Our studies demonstrate that the loss of Bmal leads to vision dysfunction possibly due to impaired rod and cone function. Furthermore, by using a mouse model of circadian rhythm dysfunction, we identified that individuals working on irregular shifts might be vulnerable to vision dysfunction, and our studies warrant timely testing of visual function and strategies for prevention of vision problems in shift workers.

Vascular and Neuronal Protection in the Developing Retina: Potential Therapeutic Targets for Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a common retinal disease in preterm babies. To prolong the lives of preterm babies, high oxygen is provided to mimic the oxygen level in the intrauterine environment for postnatal organ development. However, hyperoxia-hypoxia induced pathological events occur when babies return to room air, leading to ROP with neuronal degeneration and vascular abnormality that affects retinal functions. With advances in neonatal intensive care, it is no longer uncommon for increased survival of very-low-birth-weight preterm infants, which, therefore, increased the incidence of ROP. ROP is now a major cause of preventable childhood blindness worldwide. Current proven treatment for ROP is limited to invasive retinal ablation, inherently destructive to the retina. The lack of pharmacological treatment for ROP creates a great need for effective and safe therapies in these developing infants. Therefore, it is essential to identify potential therapeutic agents that may have positive ROP outcomes, especially in preserving retinal functions. This review gives an overview of various agents in their efficacy in reducing retinal damages in cell culture tests, animal experiments and clinical studies. New perspectives along the neuroprotective pathways in the developing retina are also reviewed.

Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension

Experimental ocular hypertension induces senescence of retinal ganglion cells (RGCs) that mimicks events occurring in human glaucoma. Senescence-related chromatin remodeling leads to profound transcriptional changes including the upregulation of a subset of genes that encode multiple proteins collectively referred to as the senescence-associated secretory phenotype (SASP). Emerging evidence suggests that the presence of these proinflammatory and matrix-degrading molecules has deleterious effects in a variety of tissues. In the current study, we demonstrated in a transgenic mouse model that early removal of senescent cells induced upon elevated intraocular pressure (IOP) protects unaffected RGCs from senescence and apoptosis. Visual evoked potential (VEP) analysis demonstrated that remaining RGCs are functional and that the treatment protected visual functions. Finally, removal of endogenous senescent retinal cells after IOP elevation by a treatment with senolytic drug dasatinib prevented loss of retinal functions and cellular structure. Senolytic drugs may have the potential to mitigate the deleterious impact of elevated IOP on RGC survival in glaucoma and other optic neuropathies.