Effect of Chondroitin Sulfate on Intraocular Pressure in Rats

Belforte, Nicolás; Sande, Pablo H.; Zavalía, Nuria de; Knepper, Paul A.; Rosenstein, Ruth E.

doi:10.1167/iovs.10-5660

Cited by 21 publications

(42 citation statements)

References 37 publications

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“…38 The role of chondroitin sulfate in systemic hypertension is also unclear, but the contribution of chondroitin sulfate to disease-associated fibrosis has been suggested in the literature. For example, (1) systemic injection of chondroitin sulfate attenuated renal fibrosis in mice undergoing unilateral ureteral obstruction; 39 (2) injection of chondroitin sulfate into the eye elevated intraocular BP; 40 and (3) chondroitin sulfate levels were elevated by 70% in the aortas of hypertensive SS rats compared with normotensive WKY rats. 41 Additionally, multiple GWAS suggestively linked an intergenic variant (rs2969070 [G]) in close proximity to CHST12 with hypertension ( P <10 -6 for MAP and pulse pressure).…”

Section: Discussionmentioning

confidence: 99%

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

et al. 2014

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Previously, we found that transferring 6.1 Mb of SS chromosome 12 (13.4-19.5 Mb) onto the consomic SS-12BN background significantly elevated mean arterial pressure in response to an 8% NaCl diet (178±7 vs. 144±2 mmHg; P<0.001). Using congenic mapping, we have now narrowed the blood pressure locus by 86% from a 6.1 Mb region containing 133 genes to an 830 kb region (chr12:14.36-15.19 Mb) with 14 genes. Compared with the SS-12BN consomic, the 830 kb blood pressure locus was associated with a Δ+15 mmHg (P<0.01) increase in blood pressure, which coincided with elevated albuminuria (Δ+32 mg/day; P<0.001), proteinuria (Δ+48 mg/day; P<0.01), protein casting (Δ+154%; P<0.05), and renal fibrosis (Δ+79%; P<0.05). Of the 14 genes residing in the 830 kb locus, 8 were differentially expressed and among these, Chst12 (carbohydrate chondroitin 4 sulfotransferase 12) was the most consistently down-regulated by 2.6 to 4.5-fold (P<0.05) in both the renal medulla and cortex under normotensive and hypertensive conditions. Moreover, whole genome sequence analysis of overlapping blood pressure loci revealed an ∼86 kb region (chr12:14,541,567-14,627,442 bp) containing single nucleotide variants near Chst12 that are unique to the hypertensive SS strain when compared to the normotensive BN, SR, and WKY strains. Finally, the 830 kb interval is syntenic to a region on human chromosome 7 that has been genetically linked to blood pressure, suggesting that insight gained from our SS-12BN congenic strain may be translated to a better understanding of human hypertension.

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Section: Discussionmentioning

confidence: 99%

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

et al. 2014

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“…Other studies have investigated the application of exogenous GAGs on IOP. Both single and chronic intracameral injections of chondroitin sulfate (CS) into the anterior chamber of rats led to a significant increase in IOP (Belforte et al, 2010). …”

Section: Ecm Manipulations That Alter Outflow Resistance In Anterior mentioning

confidence: 99%

Extracellular matrix in the trabecular meshwork: Intraocular pressure regulation and dysregulation in glaucoma

Vranka

Kelley

Acott

et al. 2015

Experimental Eye Research

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The trabecular meshwork (TM) is located in the anterior segment of the eye and is responsible for regulating the outflow of aqueous humor. Increased resistance to aqueous outflow causes intraocular pressure to increase, which is the primary risk factor for glaucoma. TM cells reside on a series of fenestrated beams and sheets through which the aqueous humor flows to exit the anterior chamber via Schlemm’s canal. The outer trabecular cells are phagocytic and are thought to function as a pre-filter. However, most of the outflow resistance is thought to be from the extracellular matrix (ECM) of the juxtacanalicular region, the deepest portion of the TM, and from the inner wall basement membrane of Schlemm’s canal. It is becoming increasingly evident that the extracellular milieu is important in maintaining the integrity of the TM. Not only have ultrastructural changes been observed in the ECM of the TM in glaucoma, and a significant number of mutations in ECM genes are known to be associated with glaucoma, but the stiffness of glaucomatous TM appears to be greater than that of normal tissue. Additionally, TGFβ2 has been found to be elevated in the aqueous humor of glaucoma patients and is assumed to be involved in ECM changes deep with the juxtacanalicular region of the TM. This review summarizes the current literature on trabecular ECM as well as the development and function of the TM. Animal models and organ culture models targeting specific ECM molecules to investigate the mechanisms of glaucoma are described. Finally, the growing number of mutations that have been identified in ECM genes and genes that modulate ECM in humans with glaucoma are documented.

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“…Moreover, injections of CS for 6 or 10 (but not 3) weeks significantly decrease electroretinographic activity as well as flash visual evoked potentials (VEPs). After 10 weeks of ocular hypertension induced by CS, a significant loss of RGCs and optic nerve fibers occurs in CS-treated eyes [1]. These results indicate that weekly intracameral injections of CS mimic central features of human primary open-angle glaucoma.…”

Section: Introductionmentioning

confidence: 57%

“…moderated glaucoma ); and iii) 10 weeks of ocular hypertension: further decrease in ERG and VEPs (vs. 6 weeks), and loss of RGCs and optic nerve fibers (i.e. advanced glaucoma ) [1].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have developed a new model of glaucoma in rats through weekly injections of chondrotin sulfate (CS) in the eye anterior chamber. Acute or chronic intracameral injections of CS significantly increase IOP as compared with vehicle-injected eyes [1]. Moreover, injections of CS for 6 or 10 (but not 3) weeks significantly decrease electroretinographic activity as well as flash visual evoked potentials (VEPs).…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Benefit of Radial Optic Neurotomy in a Rat Model of Glaucoma

et al. 2012

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Radial optic neurotomy (RON) has been proposed as a surgical treatment to alleviate the neurovascular compression and to improve the venous outflow in patients with central retinal vein occlusion. Glaucoma is characterized by specific visual field defects due to the loss of retinal ganglion cells and damage to the optic nerve head (ONH). One of the clinical hallmarks of glaucomatous neuropathy is the excavation of the ONH. The aim of this work was to analyze the effect of RON in an experimental model of glaucoma in rats induced by intracameral injections of chondroitin sulfate (CS). For this purpose, Wistar rats were bilaterally injected with vehicle or CS in the eye anterior chamber, once a week, for 10 weeks. At 3 or 6 weeks of a treatment with vehicle or CS, RON was performed by a single incision in the edge of the neuro-retinal ring at the nasal hemisphere of the optic disk in one eye, while the contralateral eye was submitted to a sham procedure. Electroretinograms (ERGs) were registered under scotopic conditions and visual evoked potentials (VEPs) were registered with skull-implanted electrodes. Retinal and optic nerve morphology was examined by optical microscopy. RON did not affect the ocular hypertension induced by CS. In eyes injected with CS, a significant decrease of retinal (ERG a- and b-wave amplitude) and visual pathway (VEP N2-P2 component amplitude) function was observed, whereas RON reduced these functional alterations in hypertensive eyes. Moreover, a significant loss of cells in the ganglion cell layer, and Thy-1-, NeuN- and Brn3a- positive cells was observed in eyes injected with CS, whereas RON significantly preserved these parameters. In addition, RON preserved the optic nerve structure in eyes with chronic ocular hypertension. These results indicate that RON reduces functional and histological alterations induced by experimental chronic ocular hypertension.

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Effect of Chondroitin Sulfate on Intraocular Pressure in Rats

Abstract: These results suggest that exogenous CS simulates the accumulation of CS in primary open-angle glaucoma and that increased amounts of CS could play a key role in the IOP dysregulation characteristic of glaucoma.

Cited by 21 publications

References 37 publications

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

Extracellular matrix in the trabecular meshwork: Intraocular pressure regulation and dysregulation in glaucoma

Therapeutic Benefit of Radial Optic Neurotomy in a Rat Model of Glaucoma

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