Novel Repair and Regeneration Therapy for Glaucoma

University of Pittsburgh researchers have discovered a novel therapy that promotes retinal ganglion cell (RGC) survival and functional restoration, as well as axon regeneration. Overexpression of the neurofilament protein, Alpha-Internexin (Ina), can reverse damage caused to RGCs and axons following an optic nerve injury. Development and optimization of this therapeutic approach could offer hope to millions of people worldwide with glaucoma and other optic nerve damage.

A novel neuroprotective treatment for optic neuropathies has been developed. AAV-Ina gene delivery can promote RGC survival in eyes compared to control eyes following optic nerve damage. Additionally, this novel treatment can also regenerate axons, offering hope to millions of patients with glaucoma. 

Description

Glaucoma, the slow progressive degeneration of RGCs and axons which make up the optic nerve, is one of the world’s leading causes of blindness. RGCs project axons and transmit visual signals to the brain. Once damaged, RGCs are irreplaceable, with loss of function leading to vision loss, severely impacting an individual’s quality of life. At present, therapies to reduce intraocular pressure can slow the progression of glaucoma. There is a pressing clinical need to develop neuroprotective treatment strategies for glaucoma and other optic neuropathies to prevent permanent vision loss. Overexpression of Ina, a protein that degrades following neuronal injury, promotes RGC survival after injury and could be a novel therapeutic strategy for optic neuropathies.

Applications

• Glaucoma
• Optic neuropathies

Advantages

Currently, there is no cure for glaucoma. While several therapeutic strategies have demonstrated RGC survival and axon regeneration, these often involve deletion of tumor suppressor genes. As a result, these therapies may promote tumorigenesis rendering them unsuitable for use in humans.

The neurofilament protein, Ina, can be administered directly to the eye, or as a nucleic acid molecule encoding Ina (e.g., transfection using an adenovirus with a capsid containing RNA encoding for Ina). This approach could lead to RGC survival and axon regeneration without the associated oncogenic risks.

Invention Readiness

Single-cell RNA sequencing of mouse retinal progenitor cells identified Ina as a protein of interest. Further experimentation confirmed that Ina was expressed in the ganglion cell layer. In animal studies, overexpression of Ina in damaged optic nerves was found to promote RGC axon regeneration and enhance RGC survival. Further testing confirmed that Ina overexpression could restore RGC function and vision in animals. Additional research is required to optimize this method, including exploring the synergistic neuroprotective effects of combining Ina with factors that can activate other key regulator pathways associated with cell growth and survival (e.g., mTOR/AKT or BMP4 pathways).

IP Status

Patent Pending

Related Publication(s)

Rao, M., Luo, Z., Liu, C.-C., Chen, C.-Y., Wang, S., Nahmou, M., Tanasa, B., Virmani, A., Byrne, L., Goldberg, J. L., Sahel, J.-A., & Chang, K.-C. (2024). Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration. Acta Neuropathologica Communications, 12(1). https://doi.org/10.1186/s40478-024-01917-6

Rao, M., Huang, Y.-K., Liu, C.-C., Meadows, C., Cheng, H.-C., Zhou, M., Chen, Y.-C., Xia, X., Goldberg, J. L., Williams, A. M., Kuwajima, T., & Chang, K.-C. (2023). Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-32702-5