advertisement
Abstract #86374 Published in IGR 21-2
Loss of PRSS56 function leads to ocular angle defects and increased susceptibility to high intraocular pressure
Labelle-Dumais C; Pyatla G; Paylakhi S; Tolman NG; Hameed S; Seymens Y; Dang E; Mandal AK; Senthil S; Khanna RC; Kabra M; Kaur I; John SWM; Chakrabarti S; Nair KSDisease models & mechanisms 2020; 13:
Glaucoma is a leading cause of blindness, affecting up to 70 million people worldwide. High intraocular pressure (IOP) is a major risk factor for glaucoma. It is well established that inefficient aqueous humor (AqH) outflow resulting from structural or functional alterations in ocular drainage tissues causes high IOP, but the genes and pathways involved are poorly understood. We previously demonstrated that mutations in the gene encoding the serine protease PRSS56 induces ocular angle closure and high IOP in mice and identified reduced ocular axial length as a potential contributing factor. Here, we show that mice also exhibit an abnormal iridocorneal angle configuration characterized by a posterior shift of ocular drainage structures relative to the ciliary body and iris. Notably, we show that retina-derived PRSS56 is required between postnatal days 13 and 18 for proper iridocorneal configuration and that abnormal positioning of the ocular drainage tissues is not dependent on ocular size reduction in mice. Furthermore, we demonstrate that the genetic context modulates the severity of IOP elevation in mutant mice and describe a progressive degeneration of ocular drainage tissues that likely contributes to the exacerbation of the high IOP phenotype observed on the C3H/HeJ genetic background. Finally, we identify five rare variants associated with human primary congenital glaucoma, a condition characterized by abnormal development of the ocular drainage structures. Collectively, our findings point to a role for PRSS56 in the development and maintenance of ocular drainage tissues and IOP homeostasis, and provide new insights into glaucoma pathogenesis.
Department of Ophthalmology, University of California, San Francisco, CA 94143, USA.
Full articleClassification:
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.4 Anterior chamber angle (Part of: 2 Anatomical structures in glaucoma)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
