Scleral calcification and photoreceptor cell death during aging and exposure to chronic stress

O'Steen, W. Keith; Brodish, A.

doi:10.1002/aja.1001890108

Cited by 13 publications

(15 citation statements)

References 18 publications

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“…The presence of Mgp expressing cells starting at the mid-sclera of the Mgp-lacZ mouse together with the fact of the high expression of this gene in cartilage, would agree with reports that the sclera of many vertebrates contains a cartilaginous cell layer (Gottlieb et al, 1990; O'Steen and Brodish, 1990; Yoshitomi and Boorman, 1990). Chondrocytes have been identified in the sclera of myopia models in chick (Kusakari et al, 1997, 2001).…”

Section: Sclera Stiffness and Myopiasupporting

confidence: 89%

“…Interestingly sclera calcification has been amply reported in the literature since as early as 1958 by David Cogan (Cogan et al, 1958), and it has been associated with aging and disease conditions since then (Patrinely et al, 1982; Wong et al, 1979). In one example in Fisher rats, the scleral cartilage is converted to bone, and 95% of the rats show a calcified sclera (O'Steen and Brodish, 1990). The authors speculate then that scleral bone formations could compromise optic circulation and influence photoreceptor death during aging.…”

Section: Sclera Stiffness and Myopiamentioning

confidence: 99%

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A single gene connects stiffness in glaucoma and the vascular system

Borrás

2017

Experimental Eye Research

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Arterial calcification results in arterial stiffness and higher systolic blood pressure. Arterial calcification is prevented by the high expression of the Matrix-Gla gene (MGP) in the vascular smooth muscle cells (VSMC) of the arteries' tunica media. Originally, MGP, a gene highly expressed in cartilage and VSMC, was found to be one of the top expressed genes in the trabecular meshwork. The creation of an Mgp-lacZ Knock-In mouse and the use of mouse genetics revealed that in the eye, Mgp's abundant expression is localized and restricted to glaucoma-associated tissues from the anterior and posterior segments. In particular, it is specifically expressed in the regions of the trabecular meshwork and of the peripapillary sclera that surrounds the optic nerve. Because stiffness in these tissues would significantly alter outflow facility and biomechanical scleral stress in the optic nerve head (ONH), we propose MGP as a strong candidate for the regulation of stiffness in glaucoma. MGP further illustrates the presence of a common function affecting key glaucomatous parameters in the front and back of the eye, and thus offers the possibility for a sole therapeutic target for the disease.

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Section: Sclera Stiffness and Myopiasupporting

confidence: 89%

Section: Sclera Stiffness and Myopiamentioning

confidence: 99%

A single gene connects stiffness in glaucoma and the vascular system

Borrás

2017

Experimental Eye Research

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“…7 In one study, metaplastic bone was detected in the sclera of the superior hemisphere in more than 95% of Fischer 344 rats. 4 Similarly, in all sheep in this study, cartilaginous metaplasia was observed only posterior to the tapetal fundus. Scrapie-infected sheep had typical neuropathologic changes of spongiform encephalopathy, but no evidence of scleral trauma, inflammation, or other abnormalities was observed histologically in the sheep.…”

Section: Discussionsupporting

confidence: 59%

Cartilaginous Metaplasia in the Sclera of Suffolk Sheep

2010

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Scleral cartilaginous metaplasia was detected by routine histologic examination of globes from 5 Suffolk sheep from a scrapie pathogenesis study. The extent of the metaplasia varied among the sheep but was always posterior to the tapetal fundus. The matrix surrounding chondrocytes stained intensely with alcian blue and was immunopositive for type II collagen. Retrospective evaluation of additional eyes from Suffolk and Cheviot sheep used in various scrapie pathogenesis studies at the authors' facility revealed similar histologic changes in 40% and 12.7% of eyes examined, respectively. The clinical significance of this previously unreported finding is unknown.Keywords cartilage, eye, metaplasia, sclera, sheepThe sclera constitutes the largest portion of the fibrous tunic of the eye and consists of a dense network of collagen fibrils, predominantly of collagen types I and III. 6 The inner portion of the sclera, or lamina fusca, also contains elastin fibers and scattered melanocytes. The sclera of many vertebrate species, such as birds, reptiles, and fish, normally contains cartilage and/or scleral ossicles. Osseous and, less often, cartilaginous metaplasia has been described in rodent sclera, 7 but the presence of scleral cartilage or cartilaginous metaplasia has not been reported in nonlaboratory domestic animal species. Animals and MethodsEyes were examined from 5 Suffolk sheep, aged 22 to 28 months, that had been part of a scrapie pathogenesis study. 2 All animals had been orally inoculated with scrapie as neonates and euthanized by barbiturate overdose when they showed advanced clinical signs of scrapie. Eyes from an additional 3 Suffolk ewes (> 24 months of age) from the National Animal Disease Center (NADC) scrapie-free flock were also examined. One globe with a segment of optic nerve of approximately 1 to 2 cm was extracted from each sheep at necropsy and immersed in 10% neutral buffered formalin. The contralateral globe was frozen for later molecular-based assays. Tissues were allowed to fix for at least 1 week, at which time a 5-mm-thick vertical section from the caudal aspect of the globe, containing retina and optic nerve, was embedded in paraffin, sectioned at 4 mm, and stained with hematoxylin and eosin (HE). For histologic examination of the contralateral eye, the globe was thawed slightly, and a similar section was trimmed, immersed in 10% neutral buffered formalin for 24 hours, and processed and stained with HE. Additional sections were stained with alcian blue at pH 1.0. Briefly, sections were stained with a 1% alcian blue solution in 0.1 N hydrochloric acid (HCl) for 30 minutes at room temperature, rinsed in 0.1 N HCl, blotted dry, and counterstained with nuclear fast red. Immunohistochemistry was performed with a monoclonal antibody against type II collagen (Millipore, Billerica, MA) at a dilution of 1:100. Briefly, sections were deparaffinized, incubated in a 0.5% pepsin solution in 5 mM HCl for 20 minutes at 37 C, incubated in 3% hydrogen peroxide, blocked in a 1.5% goat serum solution...

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“…In certain pathological conditions this may be further elaborated in the adult. In light of this it is also interesting to note that a high proportion of aging rats have cartilage formation in the sclera (O'Steen and Brodish, 1990). Thus, this may not only be a mechanism in pathological disease but may also occur due to aging.…”

Section: Discussionmentioning

confidence: 99%

The retinal pigment epithelium of the eye regulates the development of scleral cartilage

Thompson

Griffiths

Jeffery

et al. 2010

Developmental Biology

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The majority of vertebrate species have a layer of hyaline cartilage within the fibrous sclera giving an extra degree of support to the eyeball. In chicks, this is seen as a cuplike structure throughout the scleral layer. However, the mechanisms that control the development of scleral cartilage are largely unknown.Here we have studied the phases of scleral cartilage development and characterised expression profiles of genes activated during the cartilage differentiation programme. CART1 and SOX9, the earliest markers of pre-committed cartilage, are expressed in the mesenchyme surrounding the optic cup. Later AGGRECAN, a matrix protein expressed during chondrocyte differentiation, is also expressed. The expression of these genes is lost following early removal of the optic cup, suggesting a role for this tissue in inducing scleral cartilage. By grafting young retinal pigment epithelium (RPE) and retina into cranial mesenchyme in vivo, it was found that RPE alone has the ability to induce cartilage formation.There are some exceptions within the vertebrates where scleral cartilage is not present; one such example is the placental mammals. However, we found that the cartilage differentiation pathway is initiated in mice as seen by the expression of Cart1 and Sox9, but expression of the later cartilage marker Aggrecan is weak. Furthermore, cartilage forms in mouse peri-ocular mesenchyme micromass culture. This suggests that the process halts in vivo before full differentiation into cartilage, but that murine scleral mesenchyme has retained the potential to make cartilage in vitro.RA, Wnts and Bmps have been linked to the cartilage development process and are expressed within the developing RPE. We find that RA may have a role in early scleral cartilage development but is not likely to be the main factor involved.These data reveal the course of scleral cartilage formation and highlight the key role that the optic cup plays in this process. The driving element within the optic cup is almost certainly the retinal pigmented epithelium.

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Scleral calcification and photoreceptor cell death during aging and exposure to chronic stress

Cited by 13 publications

References 18 publications

A single gene connects stiffness in glaucoma and the vascular system

A single gene connects stiffness in glaucoma and the vascular system

Cartilaginous Metaplasia in the Sclera of Suffolk Sheep

The retinal pigment epithelium of the eye regulates the development of scleral cartilage

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