title: Altered expression of aquaporins 1 and 4 coincides with neurodegenerative events in retinas of spontaneously diabetic Torii rats.
abstract: Evidence is mounting that not only microangiopathy, but also neurodegenerative events occur in the retinas of humans and rodents with early diabetes. Diverse pathologies are known to alter the amount and/or location of glial expression of the water-selective channels aquaporins (AQPs) 1 and 4. However, the temporal relationships among glial activation, the altered expression of the AQP proteins and neuronal death in the retinas of diabetic animals remains to be investigated. Male spontaneously diabetic Torii (SDT) rats reportedly develop diabetes by 40 weeks of age at the latest and manifest proliferative diabetic retinopathy at 50 weeks or later. This study compared temporal changes in neuroretinal apoptosis, glial fibrillary acidic protein (GFAP) expression and the expression of AQPs 1 and 4 between SDT rat retinas and age-matched Sprague-Dawley (SD) rat retinas. Cell death was detected by terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate nick end-labeling on retinal flatmounts and activated caspase 3 immunofluorescence of retinal cryosections. The expression of GFAP and AQPs 1 and 4 was assessed by immunohistochemistry of cryosections and retinal flatmounts. Diabetes started to develop around 15 weeks in SDT rats. Apoptotic cells in the ganglion cell layer and the inner nuclear layer were significantly more numerous in 40-week-old SDT rat retinas than in either age-matched SD rat retinas or 10-week-old SDT rats. GFAP immunoreactivity was confined to the nerve fiber layer both in SD and SDT rats at 10 weeks, whereas it spanned the whole retina in SDT rats, but not in SD rats, at 40 weeks. AQP1 was expressed in the outer retina, whereas AQP4 was expressed in the perivascular and end feet of Müller cells and astrocytes in the inner retina in the control SD rats and the SDT rats at 10 weeks. The perivascular AQPs shifted from AQP4 to AQP1 in 40-week-old SDT rats that exhibited marked hyperglycemia. Thus, the development of diabetes increases neuroretinal apoptosis, and this coincides with an altered expression pattern of GFAP and water-selective channels AQPs 1 and 4 in SDT rats.
authors.affiliation: Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Masahide
authors.initials: M
authors.lastname: Fukuda
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Masanori
authors.initials: M
authors.lastname: Fuse
authors.forename: Norihide
authors.initials: N
authors.lastname: Yokoi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hamada
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
authors.forename: Akira
authors.initials: A
authors.lastname: Negi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D017209:Apoptosis; D051398:Aquaporin 1 / Q000378:metabolism*; D051401:Aquaporin 4 / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D053148:Caspase 3 / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D020287:In Situ Nick-End Labeling; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D055351:Retinal Neurons / Q000473:pathology*; D013997:Time Factors
chemical_list: D051398:Aquaporin 1; D051401:Aquaporin 4; D001786:Blood Glucose; D053148:Caspase 3; D005904:Glial Fibrillary Acidic Protein; D006442:Glycated Hemoglobin; C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; C505410:Casp3 protein, rat