Effects of Hypoxia on Retinal Pigmented Epithelium Cells: Protection by Antioxidants

Abstract

Age-related macular degeneration and other eye diseases, such as diabetic retinopathy, are probably linked to the effects of oxygen radicals derived from light or metabolic reactions. We have investigated the effects of hypoxia on bovine retinal pigmented epithelial cells (RPE) and the response of these cells to two antioxidants that have previously shown a beneficial action against free radical-linked senescent involution. The main results of the study were as follows: (i) Hypoxia induced apoptotic damage on RPE cells, with LDH leakage and ATP reduction; (ii) both vitamin C (VC) and N-acetyl-cysteine (NAC) treatment protected against hypoxia-induced apoptosis, with less DNA fragmentation. In our opinion, these findings justify further experimental and clinical work to investigate the role of hypoxia in the mechanisms of age-related RPE injury and death as well as the potential of antioxidant administration to prevent or delay retinal degenerative processes caused by oxygen-dependent pathophysiological conditions.

Retinal Thickness Measured by Spectral-Domain Optical Coherence Tomography in Eyes Without Retinal Abnormalities: The Beaver Dam Eye Study

“…Hypoxia has been found to induce apoptotic damage to RPE cells. 43 If decreased peak expiratory flow rate is a systemic marker of hypoxia in the retina, lower peak expiratory flow rate may be associated with thinning of the RPE due to cell death. However, senescence of the RPE may contribute to decreased expression of angiogenesis inhibitors, such as pigment epithelium-derived factor, further increasing the risk of neovascular age-related macular degeneration, 44 which would have the effect of thickening rather than thinning the retina.…”

Implications of DNA Leakage in Eyes of Mutant Mice

“…Skeletal muscle has also been shown to readily adapt to long-term exposure to hypoxic environments by reducing total mitochondrial content of myocytes [17]. RPE cells, by comparison, are less tolerant to hypoxia, which may explain the differential expression of the damage between the two tissues [18]. …”

Therapeutic Approach of Nanotechnology for Oxidative Stress Induced Ocular Neurodegenerative Diseases

“…Curcumin, an important antioxidant component of turmeric, protected retinal neurons in a rat model of light-induced retinal degeneration (LIRD) which exhibits a significant amount of oxidative stress and has been characterized as an AMD model (Mandal et al 2009). It was observed that N-acetyl cysteine (NAC), a thiol antioxidant, was able to protect bovine retinal RPE cells from hypoxia induced degeneration (Castillo et al 2002) and has thus been suggested to slow the development of AMD. Lutein, an antioxidant located in the lens and macula that can scavenge free radicals and filter toxic blue light, showed neuroprotection of retinal cells against retinal oxidative injury (Koushan et al 2013).…”