Enhanced Integrin α4β1–Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes

Diabetes is associated with a deficit of circulating endothelial progenitor cells (EPCs), which has been attributed to their defective mobilization from the bone marrow. The basis for this mobilization defect is not completely understood, and we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We found that culturing EPCs in high glucose media increased adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), activation of protein kinase A (PKA), and phosphorylation of α4-integrin on serine 988. This potentiated adhesion was reversed by treatment with a PKA inhibitor, overexpression of PRKAR1β, or expression of a phosphorylation-defective α4-integrin variant (α4[S988A]). Using a model of type 1 diabetes, we showed that α4(S988A)-expressing mice have more circulating EPCs than their wild-type counterparts. Moreover, diabetic α4(S988A) mice demonstrate enhanced revascularization after hind limb ischemia. Thus, we have identified a novel signaling mechanism activating PKA in diabetes (downregulation of an inhibitory regulatory subunit) that leads to deficits of circulating EPCs and impaired vascular repair, which could be reversed by α4-integrin mutation

Vision Status in Older Adults: The Brazilian Amazon Region Eye Survey

Older adults living in remote areas with limited access to health services are at higher risk to develop visual impairment and blindness. We conducted a population-based survey to determine the vision status in subjects 45 years of age and older from urban and rural areas of Parintins city, Brazilian Amazon Region. Participants underwent ophthalmic examination, including uncorrected (UCVA), presenting (PVA) and best-corrected visual acuity (BCVA). Vision status was described as lines of visual acuity (VA) impairment and lines of VA improvement from UCVA to BCVA and from PVA to BCVA in the better-seeing eye. A total of 2384 subjects were enumerated, 2041 (85.6%) were examined, with reliable VA measurements obtained from 2025 participants. Vision status in lines of VA impairment was (mean +/- standard deviation): 3.44 +/- 3.53 for UCVA, 2.85 +/- 3.52 for PVA and 1.50 +/- 3.51 for BCVA. Female gender, older age and lower education were associated with >= 6 lines of UCVA impairment. Lines of improvement >= 3 was found in 626 (30.9%) participants and associated with female gender and rural residency. In conclusion, a third of participants could have at least three lines of VA improvement with proper refraction. Strategies to improve access to eye care and affordable glasses are needed.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq, Brasilia, Brasil, Programa Ciencia sem FronteirasFundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP, Sao Paulo, BrasilSightFirst Program - Lions Club International FoundationUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Oftalmol & Ciencias Visuais, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv La Frontera, Dept Salud Publ, Temuco, ChileUniv Fed UFPA, Fac Med, Belem, PA, BrazilUniv Fed Minas Gerais, Fac Med, Dept Oftalmol & Otorrinolaringol, Belo Horizonte, MG, BrazilUniv Fed Amazonas UFAM, Fac Med, Dept Cirurgia, Div Oftalmol, Manaus, Amazonas, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Oftalmol & Ciencias Visuais, Sao Paulo, SP, BrazilCNPq: 402120/2012-4FAPESP: 2013/16397-7Lions Club International Foundation: 1758Web of Scienc