Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Abstract

Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conducted in vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabetic milieu on retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight.

Melanocortin receptor agonists MCR1‐5 protect photoreceptors from high‐glucose damage and restore antioxidant enzymes in primary retinal cell culture

“…Photoreceptors are case sensitive to high-glucose conditions [10] playing a pivotal role on diabetic retinopathy [12]. In fact, photoreceptor cell membranes are particularly rich in polyunsaturated fatty acids and extremely vulnerable to oxidative damage being the major site of superoxide generation in diabetes [34]. As MCR 1,5 modulate the nuclear transcription of the cAMP response element-binding protein (CREB) [17,35] and CREB as a redox-regulated pathway modulating MnSOD transcription [36], a possible theoretical frame, supporting this proposal, is that high-glucose exposure overexpresses MCR 1,5 and the addition of MCR 1,5 agonists lead to cAMP-PKA-CREB, increasing MnSOD transcription.…”

Organotypic retinal explant cultures as in vitro alternative for diabetic retinopathy studies

“…In vitro studies using cell culture may provide valuable insights into the cellular processes triggered by diabetic conditions, for instance into the direct cytotoxic effects of high glucose conditions (Matteucci et al, 2015). Yet, cell cultures cannot reproduce the complex interplay of different neuronal cell types that is characteristic of the retina.…”

Diabetic levels of glucose increase cellular reducing equivalents but reduce survival in three models of 661W photoreceptor-like cell injury

“…An increasingly common method of investigating the mechanisms of diabetic complications in the retina is through exploring cellular survival in in vitro retinal cell models [ 10 , 12 , 13 ]. Methods commonly used to assess the health of these in vitro models of retinal cells include neurite outgrowth assays, cell viability dyes [ 14 ], proliferation assays [ 15 ], apoptotic marker detection such as activated caspase expression [ 16 ], phosphatidylserine expression (annexin V binding) [ 17 ], and detection of DNA breakdown (TUNEL protocols) [ 18 ].…”