Purchase this article with an account.
Sara M Thomasy, Rui Chen, Laura Garzel, Katherine J. Olstad, Jun Wang, Soohyun Kim, Yumei Li, Muthuswamy Raveendran, Brooke L. Gates, J. Timothy Stout, Jeffrey Roberts, Jeffrey Rogers, Ala Moshiri; A non-human primate model of congenital heritable cataracts. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1113.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Congenital heritable cataracts are a common cause of blindness in children. Surgical management of congenital cataracts has significant morbidity; therefore new therapies to help improve outcomes are warranted. Non-human primates (NHPs) have similar postnatal visual development and ocular anatomy, particularly of the crystalline lens, to that of humans and thus are compelling models to study novel treatments. The purpose of this study was to describe the clinical characteristics, ocular histology and genetic mutation of a NHP at the California National Primate Research Center with congenital cataracts.
A 1.3-year-old female rhesus macaque (Macaca mulatta) was sedated and an ophthalmic examination was performed that included slit lamp biomicroscopy, indirect ophthalmoscopy, ultrasound pachymetry, anterior segment tomography and A-scan ultrasound. DNA was extracted from venous blood and whole genome sequencing was performed. Following euthanasia for unrelated reasons, ocular histopathology was performed on the enucleated globes.
On ophthalmic examination, hypermature cataracts and mild diffuse corneal edema were identified in both eyes (ocular uterque, OU). Additionally, the left eye was buphthalmic with a shallow anterior chamber, iris bombe and rubeosis iridis present. Intraocular pressure was 12 and 40 mm Hg in the right and left eyes, respectively; central corneal thickness was increased at 600 and 529 μm, respectively. A-scan ocular biometry confirmed the difference in globe size at 22.3 and 18.1 μm, respectively. Genetic sequencing identified a candidate mutation in CRYBB2, a βB2 crystallin highly expressed in the lens. Ocular histology confirmed hypermature cataracts characterized by the formation of Morgagnian globules, bladder cells, and vacuoles in the right eye, severe degeneration and liquefaction of cortical fibers in the left eye, and lens capsule wrinkling and rupture OU. Additionally, the left eye had a pre-iridal fibrovascular membrane with anterior synechiae and a collapsed ciliary cleft, posterior synechia and iris bombe as well as severe inner and outer retinal atrophy consistent with chronic uveitis and glaucoma.
This NHP model of congenital cataracts could not only serve as a therapeutic testing ground for novel topical treatments to ameliorate or reverse cataractogenesis, but also for optimization of gene editing in the developing eye in utero.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only