Abstract
Purpose :
Lowe syndrome is a rare X-linked recessive disorder that affects the eyes, brain, and kidneys. In particular, infants with mutations in the OCRL gene are born with cataracts and develop congenital glaucoma. Previous studies showed that mice deficient in only Ocrl (Ocrl-/-) exhibited little to no abnormalities, and those lacking in both Ocrl and Inpp5b (Ocrl-/-:Inpp5b-/-) died on embryonic day 9.5, but introduction of the human INPP5B to double-knockout mice (Ocrl-/-:Inpp5b-/-: INPP5B+/+) developed renal abnormalities seen in Lowe syndrome. However, ocular defects have yet to be described. The purpose of this study is to describe the ocular phenotypes of a Lowe syndrome mouse model (IOB) and compare to the human ocular pathology.
Methods :
Lowe syndrome IOB mouse eyes were photographed and examined for the presence of cataracts. Optical coherence tomography (OCT) imaging and tissue sectioning were performed to examine the lens and retina vasculature. An anterior chamber perfusion system was used to measure aqueous outflow rate via a computer-controlled flow pump, while a tonometer was used to measure IOP. A human Lowe syndrome patient who underwent enucleation for glaucoma was examined and compared with the mouse histology.
Results :
Cataracts were visibly present in the eyes of Lowe syndrome IOB mouse. On histology, 50% (N=8) of IOB eyes exhibited lenticular cavities, 75% showed retained nuclei in lens, and there was a significant increase (p < 0.001, student t-test) in thickness of lens basement membrane as compared to WT (N=4; control N=6). OCT and retina vessel imaging showed no significant differences between the IOB and control mice. Histology sections revealed a reduced number of ganglion cells in the retina of IOB mice. Moreover, IOB mice exhibited elevated levels of IOP than control (p = 0.01, student t-test), in addition to lower outflow rate at different IOP levels (p < 0.001, student t-test).
Conclusions :
The IOB mouse exhibits ocular defects, such as formation of cataracts and decreased aqueous outflow facility, similar to human phenotypes in Lowe syndrome patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.