Abstract: Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population. The advances in ocular genetics, retinal imaging and molecular biology, have conspired to create the ideal environment for establishing treatments for IRD, with the first approved gene therapy and the commencement of multiple therapy trials. The scope of this review is to familiarize clinicians and scientists with the current landscape of retinal imaging in IRD. Herein we present in a comprehensive and concise manner the imaging findings of: (I) macular dystrophies (MD) [Stargardt disease (ABCA4), X-linked retinoschisis (RS1), Best disease (BEST1), pattern dystrophy (PRPH2), Sorsby fundus dystrophy (TIMP3), and autosomal dominant drusen (EFEMP1)], (II) cone and cone-rod dystrophies (GUCA1A, PRPH2, ABCA4 and RPGR), (III) cone dysfunction syndromes [achromatopsia (CNGA3, CNGB3, PDE6C, PDE6H, GNAT2, ATF6], blue-cone monochromatism (OPN1LW/OPN1MW array), oligocone trichromacy, bradyopsia (RGS9/R9AP) and Bornholm eye disease (OPN1LW/OPN1MW), (IV) Leber congenital amaurosis (GUCY2D, CEP290, CRB1, RDH12, RPE65, TULP1, AIPL1 and NMNAT1), (V) rod-cone dystrophies [retinitis pigmentosa, enhanced S-Cone syndrome (NR2E3), Bietti crystalline corneoretinal dystrophy (CYP4V2)], (VI) rod dysfunction syndromes (congenital stationary night blindness, fundus albipunctatus (RDH5), Oguchi disease (SAG, GRK1), and (VII) chorioretinal dystrophies [choroideremia (CHM), gyrate atrophy (OAT)].
Background: Sodium iodate (SI) is a chemical widely applied to induce retina degeneration in animal models. SI treatment caused formation of rosettes/folds in the outer nuclear layer (ONL) of the rat retina, but it was previously unclear whether SI also forms rosettes in mice. In addition, SI induced retina degeneration was never addressed in non-separate sclerochoroid/retina pigment epithelium/retina whole mount. Here we displayed features of retina degeneration including rosette formation in mice and developed a morphological analytic assessment using sclerochoroid/retina pigment epithelium/retina whole mounts.
Methods: SI was intraperitoneally injected in Sprague-Dawley (SD) rats and C57BL/6J mice using a single dose (50 mg/kg) or with a dose range (10 to 50 mg/kg) in BALB/C mice. Rat retinas were investigated up to 2-week post-injection by histology and whole mounts, and mouse retinas were investigated up to 3-week post-injection by histology, fluorescent staining of sections and/or sclerochoroid/retina pigment epithelium/retina whole mounts for the morphological evaluations of the SI-induced retina damage.
Results: SI-induced retina damage caused photoreceptor (PR) degeneration and rosettes/folds formation, as well as retina pigment epithelium degeneration and inward migration. It displayed mixed nuclei from choroid to PRs, due to layer disorganization, as shown by single horizontal images in the sclerochoroid/retina pigment epithelium/retina whole mounts. Measurement of the PR rosette area induced by SI provided a quantitative, morphological evaluation of retina degeneration.
Conclusions: The method of non-separate sclerochoroid/retina pigment epithelium/retina whole staining and mount allows us to observe the integral horizontal view of damage from sclera to PR layers, which cannot be addressed by using sectioned and separate whole mount methods. This method is applicable for morphological evaluation of retina damage, especially in the subretinal layer.
