Biomechanics of sclera crosslinked using genipin in rabbit

Abstract

Genipin induced crosslinking of collagen can increase its biomechanical behavior by direct strengthening of the extracellular matrix in rabbit sclera, with no α-SMA expression seen in the myofibroblasts. As there is no evidence of cytotoxicity in the scleral, choroidal, and retinal cells, genipin is likely a promising agent to strengthen the weakened sclera to prevent myopic progression.

Effect of Scleral Crosslinking Using Multiple Doses of Genipin on Experimental Progressive Myopia in Tree Shrews

“…In contrast, Wang and Corpuz 32 used a much lower concentration of GEN (0.022 M) but observed a significant treatment effect on experimental myopia. Liu and Wang 49 reported a significant increase in scleral stiffness after four sub-Tenon's injections of GEN within 4 weeks in rabbit eyes. In a recent study, Hannon et al 50 reported a sustained stiffening effect in rat sclera for 4 weeks after a single retrobulbar injection of GEN at a concentration of 0.015 M and proposed its potential use as a therapeutic approach for glaucoma.…”

“… 43 , 44 Within the context of using GEN for SXL, no adverse effects have been identified based histologic investigations. 32 , 49 For instance, Wang and Corpuz 32 reported a significant thickening of scleral collagen fibrils after sub-Tenon injections of GEN in guinea pigs but no histologic damage was observed in the retina or choroid. Liu and Wang 49 found no signs of cytotoxicity in the scleral, choroidal, and retinal cells after four sub-Tenon's injections of GEN in rabbits.…”

Assessment of Visual and Retinal Function Following In Vivo Genipin-Induced Scleral Crosslinking

“…In myopia, refractive error is largely caused by scleral remodeling, which leads to axial elongation, 1 , 2 and crosslinking the posterior sclera has been hypothesized as a treatment to slow or reverse this process. 3 , 4 In glaucoma, intraocular pressure (IOP) causes excessive biomechanical strains on the optic nerve head, which is the main and early site of retinal ganglion cell (RGC) damage. It is hypothesized that reducing such excessive strains by crosslinking the posterior sclera surrounding the optic nerve may protect against RGC loss in glaucoma.…”

“…Genipin, a naturally occurring, non-photoactivated, collagen crosslinking agent extracted from the Gardenia fruit, has been previously investigated as a collagen crosslinker for ocular use. 3 , 4 , 10 – 13 Genipin acts as an anti-inflammatory and anti-angiogenic agent 14 and can induce stable crosslinks in biological tissue. 15 Genipin-induced crosslinking increases tissue stiffness by similar magnitudes as do glutaraldehyde 16 and riboflavin, 17 , 18 yet is significantly less cytotoxic than are glutaraldehyde 19 , 20 and riboflavin.…”

“…Of several studies that have evaluated genipin-induced scleral crosslinking, only two have evaluated both the efficacy and safety of genipin-induced scleral crosslinking in vivo. 4 , 12 These studies examined the biomechanical properties of genipin-stiffened scleral strips, gross ocular anatomy via slit-lamp examinations after treatment, and histological and immuno-histological sections of ocular tissues in rabbits 4 and guinea pigs. 12 These studies found that genipin successfully stiffened the sclera and did not cause any gross changes in ocular structures.…”