EXPRESSION AND LOCALIZATION OF LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 1 AND ÁLPHA 2-MACROGLOBULIN IN RETINAL AND CHOROIDAL TISSUE OF PROLIFERATIVE RETINOPATHIES

BARCELONA PF; LUNA JD; CHIABRANDO GA; JUAREZ CP; LUTTY GA; S¨¢NCHEZ MC

Fort Lauderdale, Florida, USA.

Congreso; ARVOs 2009 Annual Meeting (The Association for Research in Vision and Ophthalmology); 2009

The Association for Research in Vision and Ophthalmology

Expression and localization of low density lipoprotein receptor-related protein 1 (LRP1) and ¦Á2-Macroglobulin (¦Á2M) in retinal and choroidal tissue of proliferative retinopathies. Barcelona PF1; Luna JD2; Chiabrando GA1; Juarez CP2; Bhutto I3; McLeod DS3; S¨¢nchez MC1*; and Lutty GA3*. 1CIBICI (CONICET)-Dpto de Bioqu¨ªmica Cl¨ªnica, FCQ, UNC, Argentina. 2Dpto de Oftalmolog¨ªa, Fundaci¨®n VER, C¨®rdoba, Argentina. 3Ophthalmology, Johns Hopkins Hospital, Wilmer Eyes Inst., Baltimore, MD, US. Purpose: To determine the expression and localization of LRP1 and its ligand, ¦Á2M, in sections of eyes with proliferative diabetic (PDR) and sickle cell (SC) retinopathies. Methods: Cryopreserved tissues from eyes of normal, PDR and SC subjects were serial sectioned. APase immunohistochemistry (IHC) was performed with anti-LRP1 and anti-¦Á2M antibodies. Blood vessels were identified with anti CD-34 antibody. Mean IHC scores from the pathological and normal eyes were statistically compared. Confocal microscopy was used to analyze LRP1 and GFAP co localization. Results: LRP1 was not detected in the neural retina (NR) of normal subjects. In PDR, LRP1 expression was detected in internal limiting membrane (ILM) and in some areas of choroid, whereas ¦Á2M staining was limited to vessel wall, inner nuclear layer (INL), RPE-Bruch¡¯s membrane¨Cchoriocapillaris complex (CC) and choroidal stroma. In SC eyes, in avascular (AV) areas, LRP1 immunoreactivity was present in ILM and INL as well as RPE¨CBruch¡¯s membrane¨CCC and choroidal stroma. In a choroidal neovascularization (CNV) area, LRP1 staining was significantly decreased in NR, RPE¨CBruch¡¯s membrane-CC, and choroidal stroma. In AV area, ¦Á2M was limited to choroidal stroma, whereas in CNV area it was in RPE¨CBruch¡¯s membrane-CC and in choroidal stroma. Microdensitometric analysis revealed that NR immunostaining with both antibodies was significantly elevated (p ¡Ü 0.05) in astrocytes and ILM in PDR, whereas in SC it was significantly elevated in ILM and INL (p ¡Ü 0.05). In choroid, the pattern of LRP1 and ¦Á2M expression was not coincident. By confocal microscopy we determined that the LRP1 expression in NR of SC eyes was localized in GFAP-positive M¨¹ller cells. Conclusions: The high LRP1 expression in NR and astrocytes of PDR and SC eyes suggests that LRP1 plays an important role in human neovascular diseases associated with ischemia.Support: FONCyT, CONICET, SeCyT-UNC, IBRO-LARC, IUBMB and a gift from Himmelfarb Family Foundation in the name of Morton Goldberg, M.D.