The Woodruff School

SUMMARY

Glaucoma, which affects almost 80 million people worldwide, is the main cause of irreversible blindness. The most common type, primary open angle glaucoma (POAG), causes a gradual loss of vision by damaging retinal ganglion cells. The major risk factor for POAG is high intraocular pressure (IOP).
Current clinical treatments for POAG aim to reduce IOP, but they often have low success rates. The trabecular meshwork (TM) is a key regulator of IOP and has been shown to undergo significant changes in POAG including a loss of cells. This motivates the regeneration or restoration of the TM as a potential treatment for POAG. While TM cell therapy has shown promise in reversal of POAG pathology, previously-developed cell delivery techniques have resulted in poor cell delivery efficiency which elevates the risk of tumorigenicity and immunogenicity and undermines therapeutic potential. In addition, a lack of comprehensive characterization of the treatment effects in an appropriate POAG model is a roadblock to clinical translation.
We here tackle these shortcomings by: 1) using an optimized magnetic cell delivery method to significantly improve the specificity and efficiency of delivery of stem cells to the TM, in turn reducing the risk of unwanted side-effects, and 2) employing this optimized method to test the therapeutic capabilities of two types of cells in the current best mouse model of POAG, characterizing the morphological and functional benefits of the treatment. The central hypothesis of this work is that an optimized magnetically-driven TM cell therapy can restore IOP homeostasis while minimizing unwanted off-target cell-delivery effects.

SUBJECT:	Ph.D. Proposal Presentation

BY:	Mohammad Reza Bahrani Fard

TIME:	Thursday, April 13, 2023, 1:00 p.m.

PLACE:	IBB Building, 1128

TITLE:	Magnetic Steering to Save Sight: Trabecular Meshwork Cell Therapy as a Treatment for Primary Open Angle Glaucoma

COMMITTEE:	Dr. C. Ross Ethier, Chair (BME) Dr. Stanislav Emelianov (BME) Dr. Johnna Temenoff (BME) Dr. Cheng Zhu (ME/BME) Dr. Mark Prausnitz (ChE)

SUMMARY Glaucoma, which affects almost 80 million people worldwide, is the main cause of irreversible blindness. The most common type, primary open angle glaucoma (POAG), causes a gradual loss of vision by damaging retinal ganglion cells. The major risk factor for POAG is high intraocular pressure (IOP). Current clinical treatments for POAG aim to reduce IOP, but they often have low success rates. The trabecular meshwork (TM) is a key regulator of IOP and has been shown to undergo significant changes in POAG including a loss of cells. This motivates the regeneration or restoration of the TM as a potential treatment for POAG. While TM cell therapy has shown promise in reversal of POAG pathology, previously-developed cell delivery techniques have resulted in poor cell delivery efficiency which elevates the risk of tumorigenicity and immunogenicity and undermines therapeutic potential. In addition, a lack of comprehensive characterization of the treatment effects in an appropriate POAG model is a roadblock to clinical translation. We here tackle these shortcomings by: 1) using an optimized magnetic cell delivery method to significantly improve the specificity and efficiency of delivery of stem cells to the TM, in turn reducing the risk of unwanted side-effects, and 2) employing this optimized method to test the therapeutic capabilities of two types of cells in the current best mouse model of POAG, characterizing the morphological and functional benefits of the treatment. The central hypothesis of this work is that an optimized magnetically-driven TM cell therapy can restore IOP homeostasis while minimizing unwanted off-target cell-delivery effects.