By deciphering this network of cellular transport, Dr. Shah can target specific molecules to restore normal function and preserve vision in pediatric eye diseases.

She plans to target a signaling pathway for the resident immune cell of the retina, in order to delay cone degeneration, with the goal of improving long-term rescue following gene therapy. Together, these studies will allow for development of new strategies to extend the therapeutic window in order to treat patients with BCM at all ages (infant to adult), as well as therapy longevity for treatment of BCM.

Dr. Riaz has developed cells that can serve as an alternative to donor tissue in treating adult animals with corneal edema. The strategy includes treating corneal endothelial edema using differentiated cells in juvenile rabbits and monkeys. The knowledge gained from this project will bring us one step closer to preventing childhood blindness.

Dr. Pham is investigating the efficacy of CRISPR for treating several cellular models of pediatric ophthalmic diseases, including Leber Hereditary Optic Neuropathy (LHON), Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS), and Leigh syndrome with ophthalmoplegia. Successful demonstration of CRISPR for targeting mitochondrial DNA will open a new therapeutic avenue for these rare and incurable diseases.

Dr. Oke is developing a mathematical model based on one full year of US births that will predict whether newborn screening could prevent visual impairment in children with retinoblastoma. The result would be earlier access to care even for the most disadvantaged children within and outside of the US.

Dr. Manohar’s goal is to determine how CHD7 functions to regulate cell type differentiation in the retina, by utilizing single cell transcriptomic and chromatin binding assays in the zebrafish model. Results of these experiments will provide critical information on how CHD7 regulates retinal development, which could lead to development of new therapeutic approaches for the vision impairment associated with CHARGE syndrome.

He hopes to get fresh insight into the therapeutic approaches for RP and STGD by targeting three different nodes of ceramide metabolism - inhibiting two key enzymes generating ceramide and stimulating AdipoR1 ceramide-degrading activity to lower pathologically increased ceramides.

Dr. Krusnauskas will use RP1 gene as an example to evaluate the therapeutic potential of twinPE approach for treating inherited retinal degenerations.

Dr. Jalligampala hopes to refine the Wave1 dose/response curve; define the temporal window of efficacy using the optimal dose and evaluate its safety in intravitreal injections. To do so, she will quantify and compare across treated and untreated conditions how many rods and how much rod function is retained/recovered. The data will define key features of Wave1 administration, and issues relevant to its clinical use.

Juvenile X-linked retinoschisis is an eye disease that primarily affects male children and causes them to lose vision. In this disease, the connected layers of cells in the eye responsible for forming vision are separated by abnormal, fluid-filled pockets. This is because the function of the RS1 gene is disrupted. This disease can potentially be treated by gene therapy, which involves the delivery of the RS1 gene into the eye using engineered viruses as carriers. However, sometimes, the injections can cause undesirable side effects due to the immune system. Dr. Hsu is investigating the effect of the immune system after treatment in order to better the design of this therapy.