Decreased endostatin in db/db retinas is associated with optic disc intravitreal vascularization
Bonet, Aina (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Valença, Andreia (Universidade de Lisboa. Centre for Interdisciplinary Research in Animal Health)
Mendes-Jorge, Luisa (Universidade de Lisboa. Centre for Interdisciplinary Research in Animal Health)
Casellas, Alba (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Rodríguez Baeza, Alfonso (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Nacher García, Víctor (Universitat Autònoma de Barcelona. Departament de Sanitat i d'Anatomia Animals)
Ramos González, David (Universidade de Lisboa. Centre for Interdisciplinary Research in Animal Health)
Pampalona Sala, Judit (Universitat Autònoma de Barcelona. Centre de Biotecnologia Animal i de Teràpia Gènica (CBATEG))
Simó Canonge, Rafael (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ruberte, Jesús (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)

Date:	2021
Abstract:	Endostatin, a naturally cleaved fragment of type XVIII collagen with antiangiogenic activity, has been involved in the regulation of neovascularization during diabetic retinopathy. Here, the intracellular distribution of endostatin in healthy mouse and human neuroretinas has been analyzed. In addition, to study the effect of experimental hyperglycemia on retinal endostatin, the db/db mouse model has been used. Endostatin protein expression in mouse and human retinas was studied by immunofluorescence and Western blot, and compared with db/db mice. Eye fundus angiography, histology, and immunofluorescence were used to visualize mouse retinal and intravitreal vessels. For the first time, our results revealed the presence of endostatin in neurons of mouse and human retinas. Endostatin was mainly expressed in bipolar cells and photoreceptors, in contrast to the optic disc, where endostatin expression was undetectable. Diabetic mice showed a reduction of endostatin in their retinas associated with the appearance of intravitreal vessels at the optic disc in 50% of db/db mice. Intravitreal vessels showed GFAP positive neuroglia sheath, basement membrane thickening by collagen IV deposition, and presence of MMP-2 and MMP-9 in the vascular wall. All together, these results point that decreased retinal endostatin during experimental diabetes is associated with optic disc intravitreal vascularization. Based on their phenotype, these intravitreal vessels could be neovessels. However, it cannot be ruled out the possibility that they may also represent persistent hyaloid vessels.
Grants:	Ministerio de Ciencia e Innovación PI16/00719
Note:	Altres ajuts: acords transformatius de la UAB
Note:	Altres ajuts: Ministerio da Educação e Ciência, Portugal/SFRH/BD/95330/2013 i SFRH/BPD/102573/2014
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Experimental Eye Research, Vol. 212 (november 2021) , p. 108801, ISSN 1096-0007

DOI: 10.1016/j.exer.2021.108801
PMID: 34688624

16 p, 17.3 MB

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