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Bailey Hannon, Jieming Fu, A Thomas Read, Machelle T Pardue, C Ross Ethier; In vivo assessment of visual acuity following genipin-induced scleral crosslinking. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2024. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Scleral stiffening has been proposed as a potential therapy for glaucoma. Several studies have evaluated the use of genipin, a natural collagen crosslinker, to stiffen the posterior sclera ex vivo. However, ocular administration of genipin has not yet been studied in vivo and its effects on visual and retinal function are still unknown. Thus, we aim to assess visual and retinal function in vivo following genipin-induced crosslinking of the posterior rat sclera.
Nine male, retired breeder (9-12 months old), Brown Norway rats were anesthetized and received retrobulbar injections of 15mM genipin unilaterally (concentration based on preliminary in vivo scleral stiffening data) and vehicle contralaterally. The injected volume was 100µl per eye, divided into two 50µl injections, one to the nasal quadrant and one to the temporal quadrant. Visual function was evaluated by spatial frequency thresholds from optomotor response experiments and retinal function by full-field flash electroretinography (ERG) at 0 (pre-injection), 1, 2, and 4 weeks post-injection.
Data from vehicle and genipin-injected eyes were normalized to baseline (week 0) values for analysis. Spatial frequency thresholds of vehicle and genipin-injected eyes were not significantly different over the four weeks (Fig. 1; Two-Way repeated ANOVA, main effect of treatment: p=0.54, n=7). Additionally, ERG a- and b-wave responses were similar between the two groups of eyes over the four weeks (Fig. 2; Two-Way repeated ANOVA, main effect of treatment: a-wave amplitude, p=0.34 and implicit time (IT), p = 0.30; b-wave amp., p=0.53 and IT, p=0.97, n=7).
Our data suggest that retrobulbar injections of 15mM genipin (100µl) do not adversely affect visual or retinal function in rats for up to 4 weeks post-injection. These promising results support the safe in vivo use of genipin to modify scleral stiffness. To evaluate genipin-induced crosslinking as a potential therapy for glaucoma, future work will evaluate retinal histology following genipin injection and the persistence of genipin’s scleral stiffening effect.Support: NIH EY025286.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Figure 1: Normalized spatial frequency results. (ANOVA, Injection type: p=0.54, mean ± SD, n=7).
Figure 2: Normalized ERG results from brightest flash intensity (2.1 log cd s/m2). (ANOVA, Injection type: a-wave amp., p=0.34 and IT, p=0.30; b-wave amp., p=0.53 and IT p=0.97, mean ± SD, n ≥ 7).
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