Summary: The Li laboratory uses molecular, cellular, genetic and physiological approaches to investigate the disease mechanisms for autoimmune uveitis and retinal degeneration.

Wei Li, Ph.D.
Assistant Professor of Ophthalmology

View published research articles by this doctor in the National Library of Medicine.

Current Research Summary: My research interests focus on two areas of eye diseases: autoimmune uveitis and retinal degeneration. For autoimmune uveitis, we investigate the mechanism of autoimmune uveitis by identifying and characterizing autoantigens directly from patients with non-invasive molecular biology approaches. For retinal degeneration, we investigate the role of retinal pigment epithelium (RPE) cell phagocytosis in retinal degeneration.

Autoimmune uveitis
Autoimmune uveitis is a heterogeneous group of disorders characterized by inflammation in the eye with unknown causes. Identification of the autoantigens would markedly improve our understanding of the disease mechanisms and facilitate the diagnosis and treatment. Although several autoantigens have been identified and well characterized in animals, it is unknown whether they are the antigenic targets in clinical patients, and how many other autoantigens are yet to be identified. Traditional approaches have relied on reductive purification of eye homogenates with demonstration of uveitogenicity of the purified products in animals. These traditional approaches have problems of low efficiency and poor sensitivity. We have developed a new strategy to identify autoantigens by screening human eye phage display cDNA library using the autoantibodies in patient blood. Compared with SEREX technology (Serological identification of antigens by recombinant expression cloning), our newly-developed phage display technology has the advantages of sensitivity, efficiency, convenience for validation and minimal requirement for patient serum. This study will not only advance our understanding of uveitis mechanism, but also facilitate the development of a new diagnostic technology by using autoantigens as disease biomarkers.

Retinal degeneration
Phagocytosis is an important cellular process for many biological functions, including photoreceptor viability in the eye. For example, photoreceptor outer segment (POS) in the retina not only can convert lights to electrical signals for image formation in the brain, but also is susceptible to photo-oxidation damage. As a part of the renewal process, photoreceptors shed light-damaged POS with a circadian rhythm, which must be processed and recycled in a timely fashion. Otherwise, accumulation of shed POS in the subretinal space will cause retinal degeneration (RD). Retinal pigment epithelial (RPE) cells underneath photoreceptors within close contact to the POS play a pivotal role in POS regeneration by clarifying shed POS through phagocytosis. RPE phagocytosis mechanism is poorly defined. No phagocytic protein ligand has ever been identified. This has markedly restricted our understanding of RPE phagocytosis and its role in RD. We have developed a novel strategy to functionally clone and identify phagocytic ligands in an unbiased fashion. Several proteins have been identified with phagocytic activities.