# Cellular and Molecular Dynamics of Retinal Microglial in the Context of Photoreceptor Degeneration > **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $451,998 ## Abstract SUMMARY Many, if not most, forms of retinal degeneration involve ectopic accumulation of subretinal macrophages. However, the contribution of bona fide microglia to this immune response and their independent role in disease is poorly understood. It is now widely appreciated that macrophages in degenerating neuronal tissues are not only comprised of microglia but may also include monocyte-derived macrophages. The former are endogenous prenatal-derived cells maintained locally throughout life, whereas the latter represent transiently recruited passengers in disease states. Hence, these two distinct lineages have nonredundant activities in the disease process and should thereby be studied as distinct entities. However, distinguishing microglia is technically challenging since standard techniques such as immunolabeling, conventional reporter mice, or myeloablation bone marrow chimeras are insufficient to study these two populations. In fact, the only method to achieve such separation is through recently established Cx3cr1-CreER microglia lineage tracing mice. Yet, few studies have employed this approach, which has resulted in a knowledge gap in the field. As it is also now known that microglia are essential in establishing and preserving neuronal activity in physiological conditions, determining microglia-specific activities in retinal disease is now imperative. Using the lineage tracing approach and single- cell RNA sequencing (scRNA-seq), our lab recently identified a novel population of cytoprotective retinal microglia in photoreceptor degeneration models. We now wish to build upon these findings in our current proposal by applying novel tools to unravel these cells mechanistically, as well as to determine the significance of their cytoprotective program across etiologically distinct retinal degenerative diseases. We begin in Aim 1 by leveraging our scRNA-seq dataset to inhibit microglial chemotaxis that will allow us to determine whether cytoprotection is a subretinal-specific response. Aim 2 takes advantage of our scRNA-seq dataset as well for targeted conditional and global knockouts to establish the molecular underpinnings of microglia-mediated protection. Lastly, in Aim 3 we will apply loss- and gain-of-function studies to examine whether this cytoprotective microglial program is operative in both primary photoreceptor degeneration and retinal pigment epithelial pathology-related degeneration. In summary, our proposal is not only timely, but is also poised to unravel the innerworkings of this novel microglial population across etiologically distinct retinal degeneration models and perhaps help uncover novel therapeutic targets that can bolster their activities for vision preservation in photoreceptor degeneration. ## Key facts - **NIH application ID:** 10051963 - **Project number:** 1R01EY030906-01A1 - **Recipient organization:** DUKE UNIVERSITY - **Principal Investigator:** Daniel Raphael Saban - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $451,998 - **Award type:** 1 - **Project period:** 2020-08-01 → 2024-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10051963 ## Citation > US National Institutes of Health, RePORTER application 10051963, Cellular and Molecular Dynamics of Retinal Microglial in the Context of Photoreceptor Degeneration (1R01EY030906-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10051963. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*