Changes in the Levels of Neurospecific Proteins and Indices of Apoptosis in the Rat Cornea at Chronic Ethanol Consumption: Protective Effects of Thiamine Administration

Long-term ethanol (EtOH) consumption may induce damage to corneal nerves leading to the development of ocular diseases, vision impairments, and possible blindness. We investigated levels of neurospecific proteins and apoptotic regulators in the cornea of rats chronically exposed to ethyl alcohol and also effects of high-dose thiamine (vitamin B 1 ) administration on these indices. Albino male rats consumed 15 % (v/v) EtOH solution as a drinking liquid for 9 months. One week before the termination of the experiment, a part of EtOH-exposed rats was given thiamine per os (25 mg/kg daily for a week). The functional state of corneal nerves and their satellite cells was assessed by measuring levels of specific biomarkers (Western blot analysis), including a nuclear marker, NeuN, neurofilament heavy subunit 200 (NF-H), and tau-protein for neurons, glial fibrillary acidic protein (GFAP) for glial satellite cells, and ionized calcium binding adaptor molecule 1 (Iba-1) as microglia/macrophage specific index. The Bcl-xL/Bax ratio was measured to explore the apoptosis pathway regulation. It was found that EtOH long-lasting consumption caused a decrease in the Bcl-xL/Bax ratio and reduction in the NeuN, which was indicative of enhanced apoptosis and neurodegeneration in the injured cornea. Ethanol consumption induced accumulation of hyperphosphorylated tau protein and loss of neurofilament NF-H subunit (signs of the tauopathy development and axonal degeneration in the corneal sensory nerves). Eventually, we demonstrated that EtOH significantly upregulated corneal GFAP that might be considered as a hallmark of glia satellite cell activation in response to alcohol-induced neurodegeneration. High-dose thiamine administration noticeably alleviated neuropathological changes in the rat cornea induced by chronic EtOH ingestion through diminishing the intensity of apoptosis, reducing excessive glial activation, stabilizing the neural cell cytoskeleton, and modulating the macrophage function. Our data indicate that thiamine high-dose administration could be beneficial for minimizing the neurological consequences of long-term ethyl alcohol abuse in the cornea and may provide cost-effective and productive route to the respective interventions at ocular diseases.