Research Makes Medicine
The SupportSight Foundation continues to fund groundbreaking research that was started many years ago by the Macula Vision Research Foundation (MVRF). Our mission to save sight for millions with MacD – is all we do!
Read About the Exciting New Progress to Find a Cure for Macular Degeneration
Title: As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues
Contributing Authors: Randy Zauhar, Josef Biber, Yassin Jabri, Mijin Kim, Jian Hu, Lew Kaplan, Anna M Pfaller, Nicole Schäfer, Volker Enzmann, Ursula Schlötzer-Schrehardt, Tobias Straub, Stefanie M Hauck, Paul D Gamlin, Michael B McFerrin, Jeffrey Messinger, Christianne E Strang, Christine A Curcio, Nicholas Dana, Diana Pauly, Antje Grosche, Mingyao Li, Dwight Stambolian
The cellular events that dictate the initiation of the complement pathway in ocular degeneration, such as age-related macular degeneration (AMD), is poorly understood. Using gene expression analysis (single cell and bulk), mass spectrometry, and immunohistochemistry, we dissected the role of multiple retinal and choroidal cell types in determining the complement homeostasis. Our scRNA-seq data show that the cellular response to early AMD is more robust in the choroid, particularly in fibroblasts, pericytes and endothelial cells. In late AMD, complement changes were more prominent in the retina especially with the expression of the classical pathway initiators. Notably, we found a spatial preference for these differences. Overall, this study provides insights into the heterogeneity of cellular responses for complement expression and the cooperation of neighboring cells to complete the pathway in healthy and AMD eyes. Further, our findings provide new cellular targets for therapies directed at complement.
Apellis Announces Submission of Phase 3 data to the FDA for new drug Pegcetacoplan for Geographic Atrophy
November 3, 2022, Apellis announced plans to submit 24-month Phase 3 data to the FDA for the pegcetacoplan New Drug Application (NDA) for geographic atrophy (GA). GA is also known as advanced dry age-related macular degeneration. The longer-term data from Oaks and Derby has the potential to strengthen the product profile at launch with minimal impact to launch timelines. As previously announced, these data showed continued reduction of GA lesion growth with monthly and every-other-month pegcetacoplan treatment in both studies. The 24-month safety data were previously submitted as part of the 120-day update.
The submission of these data will be a Major Amendment to the NDA, extending the review period by three months with an expected PDUFA target action date in February 2023. We also look forward to working with global regulatory agencies to bring forward the first potential treatment for people living with GA around the world. More information can be found here.
Nov. 2021 – Exciting Progress to Find a Cure for Macular Degeneration
Title: Implication of specific retinal cell‑type involvement and gene expression changes in AMD progression using integrative analysis of single‑cell and bulk RNA‑seq profiling
Contributing Authors: Yafei Lyu, Randy Zauhar, Nicholas Dana, Christianne E. Strang, Jian Hu1, Kui Wang, Shanrun Liu, Naifei Pan, Paul Gamlin, James A. Kimble, Jeffrey D. Messinger, Christine A. Curcio, Dwight Stambolian & Mingyao Li
Age‐related macular degeneration (AMD) is a blinding eye disease with no unifying theme for its etiology. We used single‑cell RNA sequencing to analyze the transcriptomes of ~ 93,000 cells from the macula and peripheral retina from two adult human donors and bulk RNA sequencing from fifteen adult human donors with and without AMD. Analysis of our single‑cell data identified 267 cell‑type‑specific genes. Comparison of macula and peripheral retinal regions found no cell‑type differences but did identify 50 differentially expressed genes (DEGs) with about 1/3 expressed in cones. Integration of our single‑cell data with bulk RNA sequencing data from normal and AMD donors showed compositional changes more pronounced in macula in rods, microglia, endothelium, Müller glia, and astrocytes in the transition from normal to advanced AMD. KEGG pathway analysis of our normal vs. advanced AMD eyes identified enrichment in complement and coagulation pathways, antigen presentation, tissue remodeling, and signaling pathways including PI3K‑Akt, NOD‑like, Toll‑like, and Rap1. These results showcase the use of single‑cell RNA sequencing to infer cell‑type compositional and cell ‑type‑specific gene expression changes in intact bulk tissue and provide a foundation for investigating molecular mechanisms of retinal disease that lead to new therapeutic targets.
Research Grant Information
As a public charity, TSSF’s mission is to save sight for millions of people who suffer from age-related macular degeneration (AMD) and lose their precious vision. TSSF is a unique, innovative partner with the Principal Investigator (PI) and the project collaborators in ways public funding sources are not. As a private funder our position is founded on the premise that TSSF’s coveted vision research funds enhance other public and private funding resources secured by the PI and/or the project team members.
Research Makes Medicine
Vision Research Grant Program
This program supports basic and applied research directed toward understanding the pathogenesis of age-related macular degeneration (AMD or MacD). TSSF is laser-focused on the science conducted by experienced, published world-class vision researchers – Principal Investigators (PI) – who lead a team of researchers on the path to discovery. The PI’s whose body of research over time has developed and positively impacted preventative measures, treatments, and a cure for this blinding disease that affects millions of people and their families.
Preference is given to funding research programs directly related to the genetics, molecular, cellular, pathology, diagnosis, and treatment of macular degeneration that cause vision loss. The Research Makes Medicine program may also involve research related to the development of new technologies for understanding, diagnosing, and treating retinal degenerative diseases.
We also consider projects where there is a need for additional funding that will advance or enhance an existing promising research project to completion. TSSF encourages “breaking down the research silos” that exist within the scientific community. Sharing ideas and findings is critical to the discovery of new treatments and a cure for MacD. In that vein, all proposed projects must involve collaborative partnerships between institutions and/or between departments within an institution.
Proposals by invitation only.
Purpose: Outline the association between age-related macular degeneration (AMD) and functional difficulty.
Dawn taught me that research makes medicine and supporting retina research is why I continue to support their work.
John B.
