Vrathasha Vrathasha, PhD, postdoctoral researcher, has been awarded a prestigious grant from the Knights Templar Eye Foundation, Inc. for her innovative research proposal titled "Development of Mitochondrial Transplantation Therapy to Address Inherited Mitochondrial Dysfunction in Childhood-onset of LHON Optic Neurodegenerative Disease."
This grant marks an important step towards addressing Leber’s Hereditary Optic Neuropathy (LHON), a mitochondrial disorder leading to permanent blindness, predominantly caused by mutations in mitochondrial DNA. Dr. Vrathasha's work focuses on a novel therapeutic approach aimed at restoring mitochondrial function through transplantation, a method that promises to rescue retinal ganglion cell function potentially.
Mitochondrial damage leads to increased oxidative stress and selective death of RGCs, the central pathologic feature of LHON. Therefore, mitochondrial function has been a target of therapeutic intervention. Restoring mitochondrial function by transplantation is a novel therapeutic approach that can likely rescue RGC function and has the potential to benefit pediatric patients 12 years of age and younger, who account for 10% of total LHON cases. Dr. Vrathasha hypothesizes that RGCs would be able to accept healthy donor mitochondria and show improvements in the functional measures affected in LHON. Preliminary studies were conducted in iPSC-RGCs using mitochondria isolated from human skeletal muscle cells. Dr. Vrathasha’s results showed that iPSC-RGCs incubated with exogenous mitochondria accept them within 1 hour, and the uptake increases with mitochondrial dosage and incubation time. Further, oxidatively stressed iPSC-RGCs produced significantly lower reactive oxygen species following donor mitochondrial transfer. These data support that mitochondrial transplantation is worthy of further study in ophthalmic diseases—especially in childhood-onset LHON (ChO-LHON), who are reported to have a stronger chance of recovery of visual acuity. Dr. Vrathasha aims to demonstrate through studies in iPSC-RGCs from LHON patients and the LHON mouse model that mitochondrial transplantation is a viable therapy and can be used as a mitigating treatment for ChO-LHON before the onset of vision loss.
by Maressa Park