Colleen McDowell

Ophthalmology and Visual Sciences Department

Molecular pathways of glaucoma pathogenesis

cmmcdowell@wisc.edu

608-265-3996

3375 Medical Sciences Center
1300 University Ave.
Madison, WI 53706

Headshot Colleen McDowell

lab website:

https://www.ophth.wisc.edu/research/our-researchers/

Focus groups:

Immunology; Physiology

research description:

My research is dedicated to the development of novel approaches for preventing, diagnosing, and treating glaucoma. More specifically, my goal is to further understand the molecular pathways associated with the development and progression of glaucoma. My research aims to determine the molecular pathway involved in the development of elevated intraocular pressure (IOP). Elevated IOP is one of the primary risk factors in the development of glaucoma. The TM is a critical tissue involved in the outflow of aqueous humor and regulation of IOP. Changes in the ECM environment in the TM can alter the ability of aqueous humor to properly drain from the anterior chamber. The involvement of TGFβ2 signaling pathways in the regulation of the ECM in the TM has been extensively studied. Recent evidence has implicated toll-like receptor 4 (TLR4) in the regulation of ECM and fibrogenesis in other tissues such as liver, kidney, lung and skin, by inhibition of BMP and the activin membrane-bound inhibitor (BAMBI). I propose that the TLR4 signaling pathway is also involved in the regulation of the ECM in the TM. Our hypothesis is endogenous TLR4 ligands, also known as DAMPs (damage associated molecular patterns), activate TLR4 and augment TGFβ2 signaling sensitivity by downregulation of BAMBI, leading to increased ECM production in the TM and increased IOP. We are addressing this hypothesis with in vitro cell culture, in vivo mouse model methodologies, and ex vivo perfusion organ culture of human donor eyes.

ALSO A TRAINER IN THE FOLLOWING PROGRAMS: Comparative Biomedical Sciences, Neuroscience Training Program (NTP), Cellular and Molecular Pathology (CMP)

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