Luis Acaba-Berrocal, MD
Wills Eye Hospital, Philadelphia, PA
Dr. Connie Cepko received the ARVO 2025 Friedenwald Award in recognition of her groundbreaking research into the development and degeneration of the retina. The Friedenwald Award honors outstanding contributions to the basic or clinical sciences as applied to ophthalmology. Dr. Cepko is a Professor of Ophthalmology and the Bullard Professor of Genetics and Neuroscience at Harvard Medical School.
The lecture began with a video montage featuring many of Dr. Cepko’s former trainees, who shared heartfelt reflections on her impact as a mentor. They praised her passion for science, her generosity, and her dedication to nurturing the next generation of researchers. Her trainees described her as a role model who demonstrated that scientific excellence can go hand-in-hand with kindness and mentorship. A quote that resonated with many of them was, “There are many ways to succeed in science.”
Dr. Cepko opened her talk by thanking her family and the many mentors and mentees who have influenced her career. Her lecture focused on a fundamental question that has guided much of her work: How does the retina develop? She began by exploring whether there is a specific order to retinal development, using lineage-tracing experiments with retroviral vectors introduced subretinally in vivo in rats and mice. This approach enabled her team to trace the replication and differentiation of retinal progenitor cells. The key finding: retinal progenitor cells can be multipotent—some can give rise to multiple cell types, while others are more limited in potential.
This led to a deeper question: Do progenitor cells change over time? To investigate, she transplanted early-stage progenitor cells into a late-stage environment and found that the cells continued to produce early cell types. Conversely, late-stage progenitors placed in an early environment still produced late cell types. These results suggest that intrinsic factors—such as transcription factors and microRNAs—regulate the temporal identity of these cells. To better understand how progenitor cells generate the retina’s cellular diversity, Dr. Cepko focused on bipolar cells, which connect photoreceptors and exist in 15 subtypes in mice. She developed RNA FISH probes to visualize and distinguish these subtypes in vivo by targeting specific mRNAs. Her findings revealed that, in early development, the retina contains founder cells that divide to expand the retinal tissue and produce more progenitor cells. This neurogenic process begins in the center of the retina and progresses toward the periphery.
In the final portion of her talk, Dr. Cepko addressed the question: How do high-acuity areas like the fovea develop? Using chickens—which possess rod-free zones with densely packed cone cells similar to those in the human fovea—as a model, she studied how such specialized retinal regions are formed, focusing on gene expression patterns. This work provided valuable insight into foveal development in humans. She then examined whether these gene expression patterns are conserved across species, identifying specific dorsal/ventral and anterior/posterior patterning genes and enzymes. These expression patterns were found to be conserved in humans, birds, zebrafish, and even lizards—some of which have two foveas—highlighting a remarkable evolutionary conservation in retinal patterning.
Dr. Cepko concluded the lecture by showing a photo of her current lab team and expressing her gratitude to the audience.