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

Hannon, Bailey G.; Luna, Coralia; Feola, Andrew; Ritch, Matthew D.; Read, A. Thomas; Stinnett, Sandra S.; Vo, Harrison; Pardue, Machelle T.; González, Pedro; Ethier, C. Ross

doi:10.1167/tvst.9.10.8

Cited by 15 publications

(11 citation statements)

References 35 publications

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“…Technologies for specific targeting of transgene expression to the sclera and lamina cribrosa still need to be developed. The peripapillary sclera could potentially be reached by gene therapy vector via suprachoroidal or retrobulbar injections 195,233‐236 . Targeting the lamina cribrosa by gene therapy without damaging the RGC axons will be a more challenging undertaking.…”

Section: Influencing the Biomechanical Properties Of The Eyementioning

confidence: 99%

Looking into the future: Gene and cell therapies for glaucoma

Komàromy

Koehl

Park

2021

Veterinary Ophthalmology

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Glaucoma is a complex group of optic neuropathies that affects both humans and animals. Intraocular pressure (IOP) elevation is a major risk factor that results in the loss of retinal ganglion cells (RGCs) and their axons. Currently, lowering IOP by medical and surgical methods is the only approved treatment for primary glaucoma, but there is no cure, and vision loss often progresses despite therapy. Recent technologic advances provide us with a better understanding of disease mechanisms and risk factors; this will permit earlier diagnosis of glaucoma and initiation of therapy sooner and more effectively. Gene and cell therapies are well suited to target these mechanisms specifically with the potential to achieve a lasting therapeutic effect. Much progress has been made in laboratory settings to develop these novel therapies for the eye. Gene and cell therapies have already been translated into clinical application for some inherited retinal dystrophies and age‐related macular degeneration (AMD). Except for the intravitreal application of ciliary neurotrophic factor (CNTF) by encapsulated cell technology for RGC neuroprotection, there has been no other clinical translation of gene and cell therapies for glaucoma so far. Possible application of gene and cell therapies consists of long‐term IOP control via increased aqueous humor drainage, including inhibition of fibrosis following filtration surgery, RGC neuroprotection and neuroregeneration, modification of ocular biomechanics for improved IOP tolerance, and inhibition of inflammation and neovascularization to prevent the development of some forms of secondary glaucoma.

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Section: Influencing the Biomechanical Properties Of The Eyementioning

confidence: 99%

Looking into the future: Gene and cell therapies for glaucoma

Komàromy

Koehl

Park

2021

Veterinary Ophthalmology

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“…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. More recently, Hannon et al 52 reported that retrobulbar injections of GEN in rat eyes did not compromise retinal function or lead to any abnormality in retinal ganglion cell axon morphology. Furthermore, human retinal pigment epithelial cells were found to be cytocompatible with a GEN crosslinked chitosan in culture, 53 supporting the safe use of GEN for the treatment of posterior segment pathologies.…”

Section: Introductionmentioning

confidence: 99%

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

Hamdaoui

Levy

Gaonkar

et al. 2021

Trans. Vis. Sci. Tech.

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Purpose To evaluate the effect of scleral crosslinking (SXL) on slowing experimental progressive myopia in tree shrew eyes using sub-Tenon's injections of genipin (GEN) at different concentrations and number of injections. Methods Three or five sub-Tenon's injections of GEN at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day starting at 18 days of visual experience. Form deprivation (FD) myopia was induced in the injected eye between 24 and 35 days of visual experience; the fellow eye served as control. Tree shrews were randomly assigned to five experimental groups: FD ( n = 8); FD + 5 × sham injections ( n = 6); FD + 3 × GEN injections at 10 mM ( n = 6) and 20 mM ( n = 6); and FD + 5 × GEN injections at 20 mM ( n = 6). Refractive state and ocular dimensions were measured daily. Results Compared with the FD group, the sham-injected group showed a transient effect on slowing vitreous chamber elongation. With increasing GEN dose, SXL had an increasing treatment effect on slowing vitreous chamber elongation and myopia progression. In addition, SXL led to a dose-dependent shortening of the aqueous chamber depth and corneal thickening. Lens thickening was observed in the group with the highest concentration. Conclusions We have shown that SXL using GEN can slow axial elongation and myopia progression in tree shrews. The extent of this treatment effect was dose dependent. Several unexpected effects were observed (corneal thickening, decrease of the anterior chamber depth, and lens thickening), which require further optimization of the GEN delivery approach before clinical consideration. Translational Relevance The results of this preclinical study suggest that scleral crosslinking using genipin can slow myopia progression.

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“…[1] Increases in IOP induces deformation of the optic nerve head (ONH) and reduction in the retinal ganglion cells by mechanisms such as a reduction in axoplasmic ow [2], a reduction of ocular blood ow in the ONH [3], and changes induced by mechanical strain [4]. Several authors have proposed that cross-linking of the peripapillar sclera decreased the deformation of the ONH, thus reducing the deleterious changes in this area, considering the cross-linking of ONH as a potential therapeutic strategy in the management of glaucoma [5][6]. However, other authors have proposed that the induction of crosslinking could reduce ONH compliance [7], reducing axonal ow, leading to an increase in susceptibility to glaucomatous damage [8] in glaucoma models.…”

Section: Introductionmentioning

confidence: 99%

“…It has also been found that glaucoma patients exhibited a higher ocular stiffness than non-glaucoma subjects [12]. In this model, we used genipin, a natural crosslinker that has low toxicity and interesting properties, as a crosslinker agent; this agent induces corneal [13] and scleral stiffening in ex vivo and in vivo models [14], with minimal damage to the corneal endothelial and retinal cells [5][6][7][8][9][10][11][12][13][14][15], and is useful in controlling eye growth in myopia models [16]. In a clinical setting, the uses of scleral strips treated with genipin have been proposed in the control of myopia [17].…”

Section: Introductionmentioning

confidence: 99%

“…In a clinical setting, the uses of scleral strips treated with genipin have been proposed in the control of myopia [17]. Furthermore, the dosage of genipin in the rat eye has been previously characterized [18], showing a good effect as a cross-linker in the optic nerve complex; in the posterior sclera, with only one injection with no toxicity to retinal ganglion cells, there are no changes in gene expression in normal rat eyes [5]. This type of cross-linking is de ned as dark cross-linking since there is no need for an external light source in order to achieve the cross-linking effect [6].…”

Section: Introductionmentioning

confidence: 99%

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Inhibitor of Lysyl Oxidase in The Optic Nerve Head Complex Imparts Partial Protection Against Injury in Experimental Glaucoma

Cordoba¹,

Barrera²,

Pérdomo³

et al. 2021

Preprint

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Background: Glaucoma is a neurodegenerative disease with the progressive loss of retinal ganglion cells and changes in the optic nerve head (ONH). These changes are exacerbated by an increase in intraocular pressure (IOP). Methods: The effect of scleral and optic nerve softening with beta aminopropionitrile a lysyl oxidase inhibitor (BAPN) and stiffening with genipin, in a model of chronic increase of IOP was evaluated. Changes in optic nerve and retina were evaluated. H&E, Bielschowsky's silver staining and glial fibrillary acid protein (GFAP) staining was performed on optic nerve, retina and scleral structures. Changes in the expression of the Ywhab, Yhwaz (prosurvival genes), C3 complement (complement C3 inflammatory marker), CPG15 (neurite growth and neural survival gene) GFAP (glial activator marker) genes was carried out in the different groups.Results: Protective effect of BAPN was evident by the preservation of the optic nerve structure, and with the conservation of the retinal structures, while deleterious changes were evident in the stiffening of ONH complex, characterized by the increase in the glia, changes in the optic nerve, and disorganization in the retina. BAPN induced a reduction in the expression of Ywhab, Yhwaz (prosurvival genes), C3 and GFAP (inflammatory and glial marker) and CPG15. Conclusions: These findings support the critical involvement of changes in the ONH stiffness in the progression of glaucoma. The control of this variable as a regulatory mechanism in the progression of neural glaucomatous damage must be considered and would be explored as a possible intervention in glaucoma management.

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

Cited by 15 publications

References 35 publications

Looking into the future: Gene and cell therapies for glaucoma

Looking into the future: Gene and cell therapies for glaucoma

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

Inhibitor of Lysyl Oxidase in The Optic Nerve Head Complex Imparts Partial Protection Against Injury in Experimental Glaucoma

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