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Hang-Jing Wu, Sayan Paria, George Naratadam, John Kuchtey, Rachel W Kuchtey; Inner Retina Dysfunction in Microfibril Deficient Mice with Low Tension Glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2540.
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© ARVO (1962-2015); The Authors (2016-present)
Our previous identification of a disease-causing mutation in a microfibril-associated gene (ADAMTS10) in a dog glaucoma model, led us to a hypothesis that microfibril defects may cause glaucoma. Here, we investigated inner retina function in an established microfibril deficient mouse line which carries the tight skin (Tsk) mutation to test our hypothesis.
Intraocular pressure (IOP) was measured by TonoLab. Retinal nerve fiber layer (RNFL) thickness was assessed by spectral domain optical coherence tomography. Inner retinal function was evaluated at 3 months of age by positive scotopic threshold response (pSTR) in flash electroretinography (ERG) experiments. Whole mount retinas were stained for Brn3a and phosphorylated neurofilaments using SMI-31 antibody and montaged by confocal microscopy to assess retinal ganglion cell (RGC) degeneration at 16 months of age. Two-tailed Student’s t-test was used for statistical analysis. Results are presented as Mean ± SD.
IOP in 3 month old Tsk+/- mice (16.2 ± 2.9 mmHg, n = 26) was significantly lower as compared to wild type (18.7 ± 3.6 mmHg, n = 22, p < 0.05). The superior half of the RNFL was significantly thinner for Tsk+/- mice (n = 22) compared with wild type (n = 25) at 3 months of age (13.4 ± 1.3 µm vs. 14.7 ± 1.8 µm, p < 0.001). Both superior and inferior halfs of the RNFL were thinner for Tsk+/- mice (n = 16, 13.7 ± 1.6 µm superior, 14.2 ± 1.5 µm inferior) as compared to wild type (n = 27, 16.3 ± 1.2 µm superior, 17.1 ± 1.2 µm inferior) at 9 months of age (p < 10-6). The pSTR amplitude showed significant reductions in Tsk+/- mice (n = 17) compared with wild type (n = 12) at all low stimulus intensities (p < 0.05). Although density of Brn3a+ retinal ganglion cells (RGCs) was not different, increased numbers of SMI-31 positive RGCs and thinner axon bundles were apparent in retinas of Tsk+/- mice, indicating RGC degeneration.
Decreased inner retinal function occurs early in microfibril deficient Tsk mice, and is accompanied by progressive thinning of the RNFL, consistent with our hypothesis that microfibril defects cause glaucoma. At advanced age, RGC degeneration is apparent with highly persistent cell bodies in this model of low tension glaucoma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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