Project Grant R01EY039378

The National Eye Institute awarded The Research Foundation For The State University of New York $456,915 on September 1, 2026, under the Vision Research program (CFDA 93.867) to investigate molecular mechanisms of photoreceptor outer segment renewal, with performance at Syracuse, New York, through May 31, 2031.

The project uncovers fundamental molecular mechanisms underpinning the constant renewal of photoreceptor outer segments, a process critical for vision. Defects in outer segment renewal underlie many inherited retinal degenerative diseases that lead to complete blindness in humans. The research investigates how the outer segment's light-sensitive membrane material is shaped into flattened membrane discs, how these discs are structurally stabilized, and how their molecular composition is controlled. Dozens of new disc membranes are built daily at the base of each outer segment while an equal number of old discs are discarded from the tip. The project focuses on two outer segment proteins critical for these processes—PRCD and KIAA1549—both linked to retinitis pigmentosa in humans. Preliminary data show that in the absence of PRCD, newly forming discs delaminate and bleb as extracellular vesicles that accumulate in the interphotoreceptor space. The work addresses unanswered questions about how disc proteins and lipids pass through the connecting cilium and how the ciliary plasma membrane evaginates into large membrane protrusions that subsequently flatten into newly forming disc lamellae.