Pattabiraman Lab

We study age-related ocular neuropathies including Glaucoma, the association of diabetes mellitus and ocular hypertension, and age-related macular degeneration.

Ocular Hypertension and Primary Open Angle Glaucoma Research

Research

The Pattabiraman laboratory studies the pathophysiology and treatment paradigms for primary open-angle glaucoma (POAG). Glaucoma is the second leading cause of blindness around the world and POAG is the leading form of glaucoma in the United States.

Glaucoma is manifested by the loss of peripheral vision. The clinical characteristic of glaucoma is an increased cup-to-disc ratio on retinal examination, which assesses the progression of glaucoma. This increased cup to disc ratio reflects the loss of retinal ganglion cell (RGC) axons due to the degeneration of RGCs. Ocular hypertension (OHT) or elevated intraocular pressure (IOP) is believed to be responsible for the pathogenesis of POAG and reducing IOP is the only means to prevent vision loss. OHT causes the RGC death due to the biomechanical stress imparted on the retina. This loss of vision is irreversible and lowering the IOP is the only mode of reversing the vision loss or halting the progression into blindness.

Under this program, we:

i) Investigate the cellular and molecular regulators of IOP homeostasis and identify pathological mechanisms leading to elevated IOP or OHT,

ii) Develop novel ocular therapeutics to lower OHT,

iii) Study the mechanistic evidence on how OHT modulates retinal ganglion cell (RGC) survival.

iv) Differences in the structure and function of trabecular outflow tissues between people of African and European Descent.

v) Understand the role of hyperglycemia and diabetes mellitus as a risk factor for OHT

Postdoc Avinash and Graduate student Ting from the lab won the best poster awards under the postdoc and graduate student category in the Biochemistry Department Research Day in October 2022.

Our graduate student, Ting Wang's work on the role of cholesterol in regulating actin and cellular stiffness is accepted for an oral presentation at ASBMB 2022 in the SPOTLIGHT SESSION.

https://www.asbmb.org/meetings-events/2022-annual-meeting

Way to go Ting.

Padmanabhan Pattabiraman_OfficialTweeter_SocialCard.png

We will be the official tweeter at the #ASBMB2022

https://www.asbmb.org/meetings-events/2022-annual-meeting

Latest Publications

Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation

Ting Wang, Avinash Soundararajan, Jeffrey Rabinowitz, Anant Jaiswal, Timothy Osborne, Padmanabhan Paranji Pattabiraman

10.1096/fj.202301185R

Trabecular meshwork (TM) cells are highly contractile and mechanosensitive, and they aid in maintaining intraocular pressure (IOP) homeostasis. Lipids are attributed to modulating TM contractility, with poor mechanistic understanding. In this study using human TM cells, we identify the mechanosensing role of the transcription factors sterol regulatory element binding proteins (SREBPs) involved in lipogenesis. By constitutively activating SREBPs and pharmacologically inactivating SREBPs, we have mechanistically deciphered the attributes of SREBPs in regulating the contractile properties of TM. The pharmacological inhibition of SREBPs by fatostatin and molecular inactivation of SREBPs ex vivo and in vivo respectively results in significant IOP lowering. As a proof of concept, fatostatin significantly decreased the SREBPs responsive genes and enzymes involved in lipogenic pathways as well as the levels of the phospholipid, cholesterol, and triglyceride. Further, we show that fatostatin mitigated actin polymerization machinery and stabilization, and decreased ECM synthesis and secretion. We thus postulate that lowering lipogenesis in the TM outflow pathway can hold the key to lowering IOP by modifying the TM biomechanics.