Modulation of light signaling in the retina during retinal degenerative disease

Funding: “Functional plasticity in retinal degenerative disease”, R01, NEI, 2023 - 2028.

Problem/question: Many blinding diseases are initially caused by photoreceptor degeneration and various strategies are being developed to restore vision e.g. using stem cell and gene therapy approaches. However, it is now well-known that photoreceptor degeneration triggers a remodeling process of the inner retina that may corrupt retinal signaling and make these therapies ineffective. Although a lot is known about the remodeling process at structural level it has been harder to assess how it affects light signaling and vision. We ask questions about remodeling: Is it good or bad to light signaling in the retina? Does it promote or slow-down vision loss? How is light signaling changing at the level of bipolar and ganglion cells during photoreceptor degeneration? What are the molecular mechanisms underlying the functional changes in the inner retina?

Approach: We are studying a well-established animal model of retinitis pigmentosa (P23H rhodopsin knock-in mouse) together with ability to silence cones and/or rods to probe how light signaling in the inner retina is affected during rod photoreceptor degeneration. Light signaling is studied using ex vivo ERG, patch clamp retinal slice recordings from bipolar cells and large scale MEA recordings from ganglion cells. These approaches are combined with bulk and single cell RNA sequencing analysis together with immunostaining and high-resolution confocal microscopy and EM analysis of the synaptic ultrastructures.

Related publications:

UCI Ophthalmology Seminar Series Talk

Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease. Leinonen, Pham, Boyd, Santoso, Palczewski and Vinberg, 2020 in eLife

On the news:

Science Daily:

How night vision is maintained during retinal degenerative disease -

New findings in mice could inform novel treatment strategies for diseases that cause blindness

NEI News:

How is night vision maintained during retinal disease?

NEI-funded research suggests that second-order neurons in the retina play a role in preserving night vision

Moran Eye Center News Letter:

HOW IS NIGHT VISION MAINTAINED DURING RETINAL DISEASE? RESEARCH PROVIDES - NEW INSIGHT