Photoreceptor cell death is the ultimate process underlying many retinal diseases, including retinal detachment (RD). Both autophagy and inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), participate in photoreceptor cell death after RD. In this study, we examined whether TNF-α inhibition would impact the autophagy of photoreceptors and reduce the death of photoreceptors after retinal detachment (RD). RD models were created in C57BL/6J mice by a subretinal injection of 1% hyaluronic acid. The TNF-α inhibitor infliximab was administered via intraperitoneal injection two hours before RD. The levels of TNF-α and the autophagy-related proteins Atg5 and LC3B were assayed by immunofluorescence at 1 day, 3 days, and 7 days following RD. Apoptosis was examined at 3 days post-detachment via TUNEL assays. Photoreceptor cell counts were assessed at 7 days after RD. After RD, the protein levels of LC3B and Atg5 increased and reached a peak at 3 days, which decreased at 7 days. The expression of LC3B and Atg5 was prolonged and increased at a slower rate with TNF-α inhibition. The moderate augmentation and extension of autophagy through TNF-α inhibition resulted in the reduction of apoptosis and the enhancement of photoreceptor cell survival.

As the third gasotransmitter, hydrogen sulfide (H2S) plays a crucial role in the physiology and pathophysiology of many systems in the body, such as the nervous, cardiovascular, respiratory, and gastrointestinal systems. The mechanisms for its effects, including inhibiting ischemic injury, reducing oxidative stress damage, regulating apoptosis, and reducing the inflammation reaction in different systems, have not been fully understood. Recently, H2S and its endogenous synthesis pathway were found in the mammalian retina. This review describes the production and the metabolism of H2S and the evidence of a role of H2S in the retina physiology and in the different retinal diseases, including retinal degenerative diseases and vascular diseases. In the retina, H2S is generated in the presence of cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase from L-cysteine. The role of endogenous H2S and its physiologic effect in the retina are still elusive. However, strong evidence shows that retina-derived H2S might play protective or deleterious role in the pathogenesis of retinal diseases. For example, by regulating Ca2+ influx, H2S can protect retinal neurons against light-induced degeneration. H2S preconditioning can mediate the anti-apoptotic effect of retinal ganglion cells in retinal ischemia/reperfusion injury. Treatment with H2S in rats relieves diabetic retinopathy by suppressing oxidative stress and reducing inflammation. Further studies would greatly improve our understanding of the pathophysiologic mechanisms responsible for retinal diseases and the potential for the H2S-related therapy of the retinal diseases as well.

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SO2, previously known as the product of industrial waste, has recently been proven to be a novel gasotransmitter in the cardiovascular system. It is endogenously produced from the metabolism pathway of sulfur-containing amino acids in mammalians. Endogenous SO2 acts as an important controller in the regulation of many biological processes including cardiovascular physiological and pathophysiological events. Recently, the studies on the regulatory effect of endogenous SO2 on cell apoptosis and its pathophysiological significance have attracted great attention. Endogenous SO2 can regulate the apoptosis of vascular smooth muscle cells, endothelial cells, cardiomyocytes, neuron, alveolar macrophages, polymorphonuclear neutrophils and retinal photoreceptor cells, which might be involved in the pathogenesis of hypertension, pulmonary hypertension, myocardial injury, brain injury, acute lung injury, and retinal disease. Therefore, in the present study, we described the current findings on how endogenous SO2 is generated and metabolized, and we summarized its regulatory effects on cell apoptosis, underlying mechanisms, and pathophysiological relevance.

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