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The role of MMP2 for retinal regeneration in zebrafish

February 25, 2022 12:00 AM
Friedel, Kelton; Whitmore, Kimberlee; Saavedra, Jesus; Stocks, Connor; Garrett, Patrick; Morales, Justin; Sandquist, Elizabeth (Weber State University)
Faculty Advisor: Sandquist, Elizabeth (Science, Zoology)

Affecting over 30% of humans, retinal degeneration produced by conditions like age-related macular degeneration, retinitis pigmentosa and Leber congenital amaurosis is an incurable affliction primarily driven by the death of retinal photoreceptors. Though mammals are unable to combat such conditions through endogenous means, various treatments involving stem cell transplantation have begun to be developed for humans. However, these treatments face several obstacles, namely, low rates of functional stem cell integration in other mammals believed to be a product of inflammation and scarring caused during transplantation. In an effort to circumvent these issues, research in this field has begun examining the regenerative properties of zebrafish, a model organism able to regenerate a functional retina within 14 weeks post-injury. The exact mechanism for this regeneration is still unknown, but much research attributes the majority of the process to retinal Müller glia cells, multipotent stem cells that retain their multipotency in zebrafish but not mammals. The multipotency of these Müller glia allows them to continuously divide and replace all types of retinal neurons, including photoreceptors. Additionally, the integration of differentiated Müller glia into their appropriate retinal cell layer is believed to be mediated by various factors, including a series of extracellular enzymes known as matrix metalloproteinases (MMP). The present research attempts to levy the endogenous regenerative properties of the zebrafish model to understand the role of MMP2, an enzyme expressed within the Müller glia of developing zebrafish retina, in the functional regeneration and wiring of a damaged retina. Data collection is currently underway in the form of various quantitative polymerase chain reaction (qPCR) assays monitoring the expression of MMP2 in lesioned zebrafish retinas. Consistent with research examining the expression of other MMPs post-injury, MMP2 levels are expected to become overexpressed in lesioned zebrafish retina.

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