Dataset Information

Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma.

ABSTRACT:

Purpose

Scleral stiffening may protect against glaucomatous retinal ganglion cell (RGC) loss or dysfunction associated with ocular hypertension. Here, we assess the potential neuroprotective effects of two treatments designed to stiffen either the entire posterior sclera or only the sclera adjacent to the peripapillary sclera in an experimental model of glaucoma.

Methods

Rat sclerae were stiffened in vivo using either genipin (crosslinking the entire posterior sclera) or a regionally selective photosensitizer, methylene blue (stiffening only the juxtaperipapillary region surrounding the optic nerve). Ocular hypertension was induced using magnetic microbeads delivered to the anterior chamber. Morphological and functional outcomes, including optic nerve axon count and appearance, retinal thickness measured by optical coherence tomography, optomotor response, and electroretinography traces, were assessed.

Results

Both local (juxtaperipapillary) and global (whole posterior) scleral stiffening treatments were successful at increasing scleral stiffness, but neither provided demonstrable neuroprotection in hypertensive eyes as assessed by RGC axon counts and appearance, optomotor response, or electroretinography. There was a weak indication that scleral crosslinking protected against retinal thinning as assessed by optical coherence tomography.

Conclusions

Scleral stiffening was not demonstrated to be neuroprotective in ocular hypertensive rats. We hypothesize that the absence of benefit may in part be due to RGC loss associated with the scleral stiffening agents themselves (mild in the case of genipin, and moderate in the case of methylene blue), negating any potential benefit of scleral stiffening.

Translational relevance

The development of scleral stiffening as a neuroprotective treatment will require the identification of better tolerated stiffening protocols and further preclinical testing.

SUBMITTER: Gerberich BG

PROVIDER: S-EPMC9100482 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma.

Gerberich Brandon G BG Hannon Bailey G BG Brown Dillon M DM Read A Thomas AT Ritch Matthew D MD Schrader Echeverri Elisa E Nichols Lauren L Potnis Cahil C Sridhar Sreesh S Toothman Maya G MG Schwaner Stephen A SA Winger Erin J EJ Huang Hannah H Gershon Gabby S GS Feola Andrew J AJ Pardue Machelle T MT Prausnitz Mark R MR Ethier C Ross CR

Translational vision science & technology 20220501 5

<h4>Purpose</h4>Scleral stiffening may protect against glaucomatous retinal ganglion cell (RGC) loss or dysfunction associated with ocular hypertension. Here, we assess the potential neuroprotective effects of two treatments designed to stiffen either the entire posterior sclera or only the sclera adjacent to the peripapillary sclera in an experimental model of glaucoma.<h4>Methods</h4>Rat sclerae were stiffened in vivo using either genipin (crosslinking the entire posterior sclera) or a regiona ...[more]

PMID: 35536721

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Project description:BackgroundGlaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the commonest form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. The treatment can target extracellular factors such as reducing IOP, or cellular factors derived from the optic nerve itself such as blocking intracellular death signals.ObjectivesThe objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents, either topical or oral, for slowing the progression of OAG in adults.Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library, Issue 4, 2009), MEDLINE (January 1960 to January 2010), EMBASE (January 1980 to January 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2010) and ClinicalTrials.gov (http://clinicaltrials.gov). (5 January 2010). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 5 January 2010.Selection criteriaThis review was limited to randomized controlled trials (RCTs) in which topical or oral treatments were used to prevent retinal ganglion cell death. Our population of interest was adults with OAG. As the primary outcome for this review was the proportion of participants who developed any progression of visual field loss at five years post intervention, only trials with at least five years of follow-up were included.Data collection and analysisTwo review authors independently reviewed titles and abstracts from the literature searches. Full text copies of relevant or potentially relevant studies were obtained and re-evaluated for inclusion. There were no trials identified for this review, thus we performed no data extraction or meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until additional study details are provided. Reasons for excluding studies from the review were documented.Main resultsIn accordance with the selection criteria for inclusion, we identified no studies relevant for this review. The results of short-term trials and other studies are discussed in this review.Authors' conclusionsAlthough neuroprotective agents are intended to act as pharmacological antagonists to prevent cell death, the evidence that they are effective in preventing retinal ganglion cell death, and thus preserving vision in patients with OAG, has not been demonstrated. Long-term RCTs are needed to determine whether or not neuroprotective agents may be beneficial for individuals with OAG.

Dataset Information

Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma.

Purpose

Methods

Results

Conclusions

Translational relevance

Publications

Evaluation of Spatially Targeted Scleral Stiffening on Neuroprotection in a Rat Model of Glaucoma.

Similar Datasets

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