Purchase this article with an account.
Amany M Tawfik, Suchreet Mander, Sylvia B Smith, Mohamed Al-Sayed Al-Shabrawey; Blood Retinal Barrier Dysfunction in Hyperhomocysteinemia. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2342.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Homocysteine (Hcy) is a non-proteinogenic amino acid whose elevation is implicated in several human visual disorders, including diabetic retinopathy and macular degeneration. Recently we have reported functional (ERG) defects and morphological changes (including RPE) in mouse model of hyperhomocysteinemia (HHcy) due to lack of the enzyme cystathionine-β-synthase (cbs-/- and cbs+/-).The current study is aiming to investigate the role of Hcy in development and progression of age-related macular degeneration (AMD), and elucidating the underlying molecular and cellular mechanism.
To evaluate effect of HHcy on the morphology and barrier function of the RPE in a living animal, CBS deficient mice (cbs+/-) were subjected tofluorescein angiography (FA) and optical coherence tomography (OCT). Retinas harvested for cryosectioning, flatmount preparations were subjected to electron microscopic (EM) examinations of the of RPE, immunofluorescence (IMF) or light microscopy to detect blood-retinal barrier integrity (anti-ZO-1, anti-occludin)), senescence-associated beta galactosidase (S-βGal).
FA revealed neovascularization and vascular leakage in cbs+/- mice, OCT revealed decreased retinal thickness, atrophy and separation at the level of the RPE as well as drusen formation between the RPE and Bruch’s membrane. EM examination showed abnormal looking RPE with less pigmentation and accumulation of the pigmented particles in the lower part of the RPE instead of the apical part, lost apical microvilli and disturbed RPE -photoreceptor relation as well as thickened Bruch’s membrane. This was associated with decreased ZO-1/occludin levels and up-regulation of S-β Gal in RPE flatmounts.
The current study is showing evidence that excess Hcy is implicated in the development of AMD, elimination of excess Hcy could provide potential therapeutic target for AMD. Studies are underway to determine mechanisms by which HHcy triggers RPE alterations.
This PDF is available to Subscribers Only