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Kin-Sang Cho, Xin Wei, Dong Feng Chen; IGFBPL1 protects against the neuronal and vision loss in IGFBPL1-/- mice with ocular hypertension. Invest. Ophthalmol. Vis. Sci. 2019;60(9):615.
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© ARVO (1962-2015); The Authors (2016-present)
We recently reported that a novel function of insulin growth factor binding protein like 1 (IGFBPL1) on the survival and neurite outgrowth of neonatal mouse retinal ganglion cells (RGC) regulated via insulin like growth factor 1 mediated signaling pathways. We found that neonatal IGFBPL1 deficient (IGFBPL1-/-) mice have approximately 20% less of RGC comparing to wild-type control mice. In the present study, we investigate the role of IGFBPL1 protein on neuronal survival and visual performance of adult IGFBPL1-/- mice with or without elevated intraocular pressure (IOP).
RGC densities of 1, 2 and 7 months-old IGFBPL1-/- mice were determined by Brn3a immunolabeling in retinal flat-mounts. To induce elevation of IOP, two micro liter of polystyrene microbeads (MB; 5x10^6/ml) were injected into the anterior chamber of unilateral eye of adult male and female IGFBPL1-/- mice. IGFBPL1 recombinant protein or sterile saline as a control was administered by intravitreal injection at 3, 7 and 17 days post-MB injection. At 4 weeks post-MB injection, two investigators recorded the optomotor response of contrast sensitivity and visual acuity of mice in a masked fashion. The mice were sacrificed and the retinas were flat-mounted and processed for Brn3a immunolabeling to reveal surviving RGC. Student's t-test was used for statistical analysis.
Our data showed that absence of IGFBPL1 led to progressive loss of RGC in IGFBPL1-/- mice. Upon a transient elevation of IOP, we detected a significant decline of visual performance and RGC loss in adult IGFBPL1-/- mice. IGFBPL1 treatment significantly improved the visual performance (P<0.05) and RGC survival (P<0.05) in wild-type and IGFBPL1-/- mice with ocular hypertension.
IGFBPL1 has been known to express strongly in embryonic retina and barely detect in adult retina. Our results showed that lack of IGFBPL1 during embryonic stage induces progressive degeneration of RGC in IGFBPL1-/- mice. Administration of IGFBPL1 protects against the RGC and vision loss in mouse with ocular hypertension. Overall, IGFBPL1 is an important neuroprotective agent in retina undergoing progressive degeneration, such as in glaucoma.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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