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Michael Elliott

Role of caveolin-1 in neurovascular inflammation in the retina. Neurovascular inflammatory processes are critical events in a host of retinal diseases including age-related macular degeneration and diabetic retinopathy. We have found that caveolin-1, a protein abundantly expressed in retinal vascular cells and the primary retinal glia (Müller glia), plays important roles in the maintenance of the blood-retinal barrier and in control of innate inflammatory responses. Intriguingly, caveolin-1 promotes activation of Toll-like receptor-4 signaling in the retina. We are currently examining a novel molecular mechanism for this control that involves regulation of the stability of TNF Receptor Associated Factor-3 (TRAF3).

Caveolae as mechanosensors for intraocular pressure homeostasis. Glaucoma is a major cause of blindness worldwide with primary open angle glaucoma being the most prevalent form. The primary risk factor in glaucoma, intraocular pressure, is regulated by control of the rate of drainage of aqueous fluid from the eye from a unique vascular network called the conventional outflow pathway. While the molecular mechanisms that control conventional outflow are not well understood, homeostatic responses of conventional outflow cells to mechanical stimulation are crucial. Polymorphisms in the CAV1/2 genes, which encode essential proteins for a putative membrane mechanical sensor, caveolae, associate with POAG and elevated IOP. Genetic deletion of CAV1 in mice ablates caveolae, resulting in ocular hypertension due to functional defects in conventional outflow function. The mechanism for this defect and the connection between disease-associated polymorphisms and caveolae function are not understood. This project addresses these important knowledge gaps.

Novel regulators of ocular wound healing. The clear cornea is the outermost structure of the eye, which transmits light to the inside of the eye.  The cells responsible for maintaining the corneal surface are called limbal stem cells.  These cells normally divide and proliferate to repopulate the cornea as well as heal the surface after a wound.  Without proper wound healing, corneal blindness can result.  We have found that caveolin-1 regulates the process of wound healing and that loss of this protein in a knockout mouse model leads to faster healing.  Evidence suggests that caveolin-1 works by regulating stem cell proliferation.  Our intent is to better understand this process and develop medications that can mimic the loss of caveolin-1 and accelerate wound healing.