Autophagic Regulation of Eye Interaction

Herpes simplex virus type-1 (HSV-1) provides a valuable tool for identifying new cellular mechanisms that safeguard the cornea and innervating sensory nerves. HSV-1 infections in the cornea can lead to epithelial damage, chronic inflammation, and impairment of sensory nerve fibers, ultimately resulting in blindness. In recent research, we investigated the role of the optineurin (OPTN) gene in HSV-1 infection and unexpectedly found an inverse correlation between OPTN expression and the severity of herpes stromal keratitis (HSK) in experimental mice. Our published findings also demonstrated that OPTN dysfunction leads to accelerated loss of central nervous system (CNS) neurons after HSV-1 eye infection. OPTN-/- animals show issues with the development of adaptive immune responses and deficiencies in autophagic degradation of HSV-1 proteins. Notably, OPTN, an autophagy receptor, is known for regulating the transport of ubiquitinated proteins and damaged mitochondria to autophagosomes for degradation. Our preliminary findings using OPTN-/- animals indicate that the loss of OPTN directly correlates with the loss of corneal nerve functions, including mitochondrial dysfunction, underscoring its unrecognized significance in herpes neurotrophic keratitis (HNK) and other sensory nerve complications, such as dry eye disease (DED). Based on our recently published and preliminary data, we propose a stimulating hypothesis that OPTN plays a central yet poorly understood role in mitigating the severity of herpetic eye disease. To deepen our understanding, we plan to comprehensively investigate the impact of OPTN on herpetic disease in the cornea.