Retinoic acid signals the direction of ocular elongation in the guinea pig eye

McFadden, Sally A; Howlett, Marcus H. C.; Mertz, James R.

doi:10.1016/j.visres.2003.11.002

Cited by 182 publications

(157 citation statements)

References 26 publications

Supporting

Mentioning

151

Contrasting

Order By: Relevance

“…In postnatal development, the retina adjusts ocular focus by altering extensibility of the sclera, and the RPE has been postulated, but not proven, to relay these regulatory signals from the retina (2). Retinoic acid in the retina is markedly decreased during lens-induced hyperopia in mammals (32), and a similar decrease might also occur in nanophthalmos. Because retinoic acid and 11-cis retinal both arise from vitamin A and undergo metabolism in the RPE, the mechanism used to downregulate retinoic acid synthesis could have secondary effects on the recycling of visual pigment.…”

Section: Discussionmentioning

confidence: 99%

Extreme hyperopia is the result of null mutations inMFRP, which encodes a Frizzled-related protein

Sundin

Leppert

Silva

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

165

131

View full text Add to dashboard Cite

Nanophthalmos is a rare disorder of eye development characterized by extreme hyperopia (farsightedness), with refractive error in the range of ؉8.00 to ؉25.00 diopters. Because the cornea and lens are normal in size and shape, hyperopia occurs because insufficient growth along the visual axis places these lensing components too close to the retina. Nanophthalmic eyes show considerable thickening of both the choroidal vascular bed and scleral coat, which provide nutritive and structural support for the retina. Thickening of these tissues is a general feature of axial hyperopia, whereas the opposite occurs in myopia. We have mapped recessive nanophthalmos to a unique locus at 11q23.3 and identified four independent mutations in MFRP, a gene that is selectively expressed in the eye and encodes a protein with homology to Tolloid proteases and the Wnt-binding domain of the Frizzled transmembrane receptors. This gene is not critical for retinal function, as patients entirely lacking MFRP can still have good refraction-corrected vision, produce clinically normal electroretinograms, and show only modest anomalies in the dark adaptation of photoreceptors. MFRP appears primarily devoted to regulating axial length of the eye. It remains to be determined whether natural variation in its activity plays a role in common refractive errors.eye ͉ genetics ͉ morphology ͉ nanophthalmos

show abstract

Section: Discussionmentioning

confidence: 99%

Extreme hyperopia is the result of null mutations inMFRP, which encodes a Frizzled-related protein

Sundin

Leppert

Silva

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

165

131

View full text Add to dashboard Cite

show abstract

“…Choroidal synthesis of atRA is modulated during periods of visually induced changes in ocular growth and has pronounced effects on scleral extracellular matrix metabolism in chicks (9,12), guinea pigs (11), and marmosets (10). Based on estimated endogenous concentrations of atRA in the choroid (ϳ4 ϫ 10 Ϫ9 to ϳ3 ϫ 10 Ϫ8 M) and the calculated half-maximal effective concentration (EC 50 ) of atRA on inhibition of scleral proteoglycan synthesis (8 ϫ 10 Ϫ9 M), we speculate that choroidally derived atRA is transported to the sclera where it inhibits proteoglycan synthesis, resulting in a slowing of ocular growth (13).…”

mentioning

confidence: 99%

Identification of Apolipoprotein A-I as a Retinoic Acid-binding Protein in the Eye

Summers¹,

Harper²,

Feasley

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

All-trans-retinoic acid may be an important molecular signal in the postnatal control of eye size. The goal of this study was to identify retinoic acid-binding proteins secreted by the choroid and sclera during visually guided ocular growth. Following photoaffinity labeling with all-trans-[11,12-3 H]retinoic acid, the most abundant labeled protein detected in the conditioned medium of choroid or sclera had an apparent M r of 27,000 Da. Following purification and mass spectrometry, the M r 27,000 band was identified as apolipoprotein A-I. Affinity capture of the radioactive M r 27,000 band by anti-chick apolipoprotein A-I antibodies confirmed its identity as apolipoprotein A-I. Photoaffinity labeling and fluorescence quenching experiments demonstrated that binding of retinoic acid to apolipoprotein A-I is 1) concentration-dependent, 2) selective for all-trans-retinoic acid, and 3) requires the presence of apolipoprotein A-I-associated lipids for retinoid binding. Expression of apolipoprotein A-I mRNA and protein synthesis were markedly upregulated in choroids of chick eyes during the recovery from induced myopia, and apolipoprotein A-I mRNA was significantly increased in choroids following retinoic acid treatment. Together, these data suggest that apolipoprotein A-I may participate in a regulatory feedback mechanism with retinoic acid to control the action of retinoic acid on ocular targets during postnatal ocular growth.

show abstract

“…Therefore, myopia might be triggered at the level of photoreceptors or visual metabolism. The level of retinoic acid in retinal and choroid layers has also been shown to change significantly in animal myopia models (Seko et al, 1998;Bitzer et al, 2000;Mertz and Wallman, 2000;McFadden et al, 2004). Thus, it is speculated that retinoid acid might provide signals to modulate eye growth and play a role in the onset and development of myopia (Morgan, 2003).…”

Section: Introductionmentioning

confidence: 99%

Investigation of the association between all-trans-retinol dehydrogenase (RDH8) polymorphisms and high myopia in Chinese

Wang

Shen

et al. 2010

J. Zhejiang Univ. Sci. B

View full text Add to dashboard Cite

Retinoic acid level in the retina/choroid is altered in induced myopia models. All-trans-retinol dehydrogenase (RDH8) is an important enzyme of retinoic acid metabolism. This study aimed to investigate the association of the RDH8 gene with high myopia. Three single nucleotide polymorphisms (SNPs) [RDH851 (rs2233789), RDH8E5a (rs1644731), and RDH855b (rs3760753)] were selected, based on the linkage disequilibrium pattern of RDH8 from a previous study, and genotyped for 160 Han Chinese nuclear families with highly myopic (−10 diopters or worse) offspring as well as in an independent group with 166 highly myopic cases (−10 diopters or worse) and 211 controls. Family-based association analysis was performed using the family-based association test (FBAT) package, and genotype relative risk (GRR) was calculated using the GenAssoc program. Population-based association analysis was performed using Chi-square test. These SNPs were in linkage equilibrium with each other. SNPs RDH851 (rs2233789) and RDH8E5a (rs1644731) both did not show association with high myopia. SNP RDH855b (rs3760753) demonstrated significant association (P=0.0269) with a GRR of 0.543 (95% confidence interval=0. 304-0.968, P=0.038). The association became statistically insignificant, however, after multiple comparison correction. Haplotype analysis did not show a significant association either. Population-based association analysis also showed no significant association (P>0.05). Our family-and population-based data both suggest that the RDH8 gene is unlikely to be associated with high myopia in Chinese.

show abstract

Retinoic acid signals the direction of ocular elongation in the guinea pig eye

Cited by 182 publications

References 26 publications

Extreme hyperopia is the result of null mutations inMFRP, which encodes a Frizzled-related protein

Extreme hyperopia is the result of null mutations inMFRP, which encodes a Frizzled-related protein

Identification of Apolipoprotein A-I as a Retinoic Acid-binding Protein in the Eye

Investigation of the association between all-trans-retinol dehydrogenase (RDH8) polymorphisms and high myopia in Chinese

Contact Info

Product

Resources

About