Thesis Seminars

Andrea Campbell - PhD Candidate, Neuroscience Graduate Program

Visual impairment affects over 2.2 billion people worldwide, with retinal diseases (RDs) like age-related macular degeneration (AMD) and retinitis pigmentosa (RP) as significant contributors to this impairment. These diseases lead to the degeneration of photoreceptor cells, which lack a natural regenerative capacity in humans. Current treatments primarily aim to slow disease progression, underscoring a critical need for regenerative strategies focused on restoring vision. Photoreceptor precursor cells (PRPCs) derived from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) are promising candidates for cell replacement therapies. However, immune-mediated rejection and inflammation remain significant barriers to their success. To address these challenges without relying on prolonged immune suppression, this study evaluates two complementary strategies: (1) short-term systemic immune suppression and (2) co-transplantation of PRPCs with regulatory T cells (T-regs).

Aim 1 evaluates the efficacy of short-term immune suppression in promoting PRPC survival. Prolonged immune suppression increases risks such as infections and systemic toxicity. Inspired by transient protocols in retinal pigment epithelium (RPE) transplantation, this study hypothesizes that a short-term immunosuppressive regimen can promote PRPC survival while minimizing adverse effects. Advanced adaptive optics scanning laser ophthalmoscopy (AOSLO) will facilitate non-invasive, longitudinal imaging of PRPC survival and host immune responses at cellular resolution.

Meeting ID: 944 0302 2429
Passcode: 903589

Aim 2 examines the co-transplantation of PRPCs with T-regs to locally modulate immune responses. T-regs play a key role in immune tolerance and may provide a localized, cellular alternative to pharmacological immune suppression. By dampening inflammation and inhibiting cytotoxic T-cell activity, T-regs could enhance PRPC survival. Using fluorescent reporters and high-resolution imaging, this study will track immune activity, T-reg function, and PRPC survival in real-time, assessing the potential of T-regs to mitigate rejection.

This research integrates cutting-edge imaging technologies, fluorescent reporters, and an NHP model that closely mimics human retinal anatomy, physiology, and immune responses. By leveraging these innovations, the study seeks to advance regenerative therapies for retinal diseases, providing insights into immune modulation and stem cell-based interventions. Success in these strategies could pave the way for safer and more effective treatments for RD patients, addressing an unmet medical need and establishing a framework for future cell-based therapies in ophthalmology.

 Jan 13, 2025 @ 11:00 a.m.
 Medical Center | K307 (3-6408)