[CCoE Notice] BIOE MS Thesis Defense

[Knudsen, Rachel W]

[cid:1cae5661-8534-4fd1-a2a9-5fbf7c5f64a1]


Monday, December 2nd, 2019 1:00 PM

ENGINEERING II, ROOM W205


[cid:4a8b0163-b188-41d0-9c5e-7a488e950fa3]

Haarthi Sakthivel

MS Thesis Defense

Dr. Muna Naash, Faculty Advisor


“Secondary effects associated with photoreceptor degeneration due to mutations in peripherin 2.”


Abstract

Peripherin 2 (Prph2, also known as, RDS) is a photoreceptor-specific transmembrane glycoprotein and is a building block of retinal photoreceptor outer segments (OS). Mutations in Prph2, such as Prph2Y141C, Prph2C213Y, Prph2K153del, and Prph2R172W, cause disease in rods and cones in both patients and animal models. However, as the pathology progresses, secondary effects in neighboring tissues can also occur. However, these secondary effects have not been thoroughly investigated. We here hypothesize that aberrant Prph2 complexes which occur in the mutants are not properly digested in the RPE, leading to RPE toxicity, induction of immune responses, and other defects in surrounding tissues.

Functional and structural changes associated with expression of mutant Prph2 were assessed by electroretinography, fundus imaging and transmission electron microscopy. Induction of an immune response was studied by immunofluorescence where we observed macrophages engulfing diseased RPE cells. In mutant models, we found gradual reductions in c-wave responses, a measure of the retinal pigment epithelium health (RPE), accumulation of abnormal vacuoles in the RPE, displacement of melanin pigment, dilation of Bruch’s membrane, and leakage of retinal blood vessels. Undigested OS debris and macrophages were also found in the RPE, showing delay of phagocytosis and induction of an immune response. These data indicate that even though Prph2 is a photoreceptor-specific protein and mutations cause drastic photoreceptor degeneration, their secondary effects are equally, if not more detrimental, to the health of the retina.

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