Retinal Nerve and Vascular Changes in Prediabetes.

OBJECTIVE: This study aimed to observe vascular and neuroretinal alterations in people with prediabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT)] and normal glucose metabolism. METHODS: A total of 21 patients with prediabetes (42 eyes) and 20 healthy controls (40 eyes) participated in our study. All patients underwent a complete eye examination [including fundus fluorescein angiography (FFA) and optical coherence tomography (OCT)] and a related general examination (complete biochemical analysis, routine blood tests, and glycosylated hemoglobin). RESULTS: On FFA, no patients in either group showed any microvascular alterations. The total peripapillary retinal nerve fiber layer (pRNFL) in the prediabetic group was significantly thinner than that in the healthy control group (p < 0.0001). Only the temporal pRNFL thickness was significantly less in patients with prediabetes compared to the normal people. There was no significant difference in the thickness of retina in the range of 1 mm diameter of macular fovea (p = 0.286), but in the prediabetic group, the macular retinal thickness within the diameter of 6 mm in nasal side (p < 0.0001), superior side (p < 0.0001), temporal side (p = 0.008), and inferior side (p = 0.001) were lower than that in the control group. CONCLUSION: In the prediabetic group, there was no microvascular alterations, but the total pRNFL and the temporal pRNFL was significantly thinner, and the macular retinal thickness within the diameter of 6 mm in the nasal, temporal, and inferior side were lower than that in the healthy control group. These data confirm neuroretinal alterations in prediabetes prior to microvascular injury.

Inhibition of retinal ganglion cell apoptosis: regulation of mitochondrial function by PACAP.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous peptide with neuroprotective effects on retinal neurons, but the precise mechanism underlying these effects remains unknown. Considering the abundance of mitochondria in retinal ganglion cells (RGCs), we postulate that the protective effect of PACAP is associated with the regulation of mitochondrial function. RGC-5 cells were subjected to serum deprivation for 48 hours to induce apoptosis in the presence or absence of 100 nM PACAP. As revealed with the Cell Counting Kit-8 assay, PACAP at different concentrations significantly increased the viability of RGC-5 cells. PACAP also inhibited the excessive generation of reactive oxygen species in RGC-5 cells subjected to serum deprivation. We also showed by flow cytometry that PACAP inhibited serum deprivation-induced apoptosis in RGC-5 cells. The proportions of apoptotic cells and cells with mitochondria depolarization were significantly decreased with PACAP treatment. Western blot assays demonstrated that PACAP increased the levels of Bcl-2 and inhibited the compensatory increase of PAC1. Together, these data indicate protective effects of PACAP against serum deprivation-induced apoptosis in RGCs, and that the mechanism of this action is associated with maintaining mitochondrial function.