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Estrogens reduce the expression of YKL-40 in the retina: implications for eye and joint diseases
Jean-Marie Rakic1, Vincent Lambert, Manuel Deprez
1Department of Ophthalmology, University Hospital, Sart-Tilman, Liège, Belgium. jmrakic@chu.ulg.ac.be
Purpose:
To identify modifications in the gene expression profile of the ocular posterior segment in ovariectomized (OVX) mice with and without substitutive estradiol therapy and to select differentially expressed genes that could be relevant to the natural history of human age-related macular degeneration (AMD).
Methods:
Chorioretinal tissues from two groups of 25 treated and untreated OVX mice were analyzed by using cDNA array technology. The expression level of selected genes was confirmed in triplicate by RT-PCR and related to the estrogenic status of the animals. Expression of the YKL-40 gene was further investigated in intact or diseased human retinas and in a murine model of experimental choroidal neovascularization (CNV), using laser pressure catapulting.
Results:
Of the approximately 10,000 genes screened, only YKL-40 expression was significantly downregulated by 17-beta-estradiol. YKL-40 was expressed in intact human neural retina and in the RPE. The expression of YKL-40 was upregulated in experimental CNV and in neovascular membranes extracted from patients affected by the exudative form of AMD.
Conclusions:
These observations indicate that YKL-40 expression in the retina is modulated by serum levels of estradiol. This protein could be relevant to the development of AMD and is also a new mediator to take into account when evaluating the broad consequences of hormonal replacement therapy.
Insights
Estradiol therapy downregulates YKL-40 gene expression in the eye. This finding is relevant to age-related macular degeneration (AMD) and hormonal replacement therapy effects.
Area of Science:
- Ophthalmology
- Endocrinology
- Genetics
Background:
- Ovariectomy (OVX) in mice mimics menopause, affecting ocular tissues.
- Estrogen levels influence various physiological processes, including those in the eye.
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
Purpose of the Study:
- To investigate gene expression changes in the posterior eye segment of OVX mice.
- To determine the effect of estradiol therapy on gene expression.
- To identify genes relevant to age-related macular degeneration (AMD) pathogenesis.
Main Methods:
- Gene expression profiling using cDNA array technology in OVX mice.
- Validation of gene expression using RT-PCR.
- Investigation of YKL-40 in human retinas and a murine model of choroidal neovascularization (CNV).
Main Results:
- YKL-40 gene expression was significantly downregulated by 17-beta-estradiol in OVX mice.
- YKL-40 was detected in human neural retina and retinal pigment epithelium (RPE).
- YKL-40 expression was upregulated in experimental CNV and exudative AMD neovascular membranes.
Conclusions:
- Retinal YKL-40 expression is modulated by serum estradiol levels.
- YKL-40 may play a role in the development of AMD.
- YKL-40 is a potential mediator in the context of hormonal replacement therapy.
