Interphotoreceptor matrix based biomaterial: Impact on human retinal progenitor cell attachment and differentiation.

While cell transplantation therapies show great promise as treatments for retinal degeneration, the challenge of low cell survival upon transplantation motivates exploration of materials that may serve as cell delivery vehicles and promote survival and differentiation. In this study, we explored the native matrix that surrounds the outer segments of photoreceptors and promotes their homeostasis, interphotoreceptor matrix (IPM), as a substrate for human retinal progenitor cells (hRPCs). Bovine IPM was characterized to determine its structure and biochemical composition, and processed to develop substrates for cells. Cell viability, morphology, proliferation and expression of photoreceptors marker genes were studied on IPM-based substrates in vitro. We explored different preparations of IPM as a scaffold. Lectin staining revealed that a distinct honeycomb structure of native IPM is lost during centrifugation to prepare a more concentrated suspension of matrix. Biochemical analysis of bovine IPM indicated presence of glycosaminoglycans and proteins. IPM mediated hRPC attachment and spreading with no signs of cytotoxicity. Cells proliferated more on native IPM substrates compared to IPM that was centrifuged to create a concentrated suspension. Cells cultured on IPM substrates expressed markers of photoreceptors: rhodopsin, NRL and ROM1. Together this data supports further exploration of IPM as a tool for retinal tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 891-899, 2018.

Incremental prognostic value of kidney function decline over coronary artery disease for cardiovascular event prediction after coronary computed tomography.

It is unknown whether mild chronic kidney disease (CKD) is associated with adverse cardiovascular (CV) prognosis after accounting for coronary artery disease (CAD). Here we evaluated the interplay between CKD and CAD in predicting CV death or myocardial infarction (MI) and all-cause death. We included 1541 consecutive patients in the Partners registry (mean age 55 years, 43% female) over 18 years old with no known prior CAD who underwent coronary computed tomography angiography (CCTA). The results of CCTA were categorized as normal, nonobstructive (under half), or obstructive (half and over). Overall, 653 of the patients had no CAD, 583 had nonobstructive CAD, and 305 had obstructive CAD, while 1299 had eGFR over 60 ml/min per 1.73 m(2) and 242 had an eGFR under this value. The presence and severity of CAD was significantly associated with an increased rate of CV death or MI and all-cause death, even after adjustment for age, gender, symptoms, and risk factors. Similarly, reduced eGFR was significantly associated with CV death or MI and all-cause death after similar adjustment. The addition of reduced GFR to a model which included both clinical variables and CCTA findings resulted in significant improvement in the prediction of CV death or MI and all-cause death. Thus, among individuals referred for CCTA to evaluate CAD, renal dysfunction is associated with an increased rate of CV events, mainly driven by an increase in the rate of noncoronary CV events. In this group of patients, both eGFR and the presence and severity of CAD together improve the prediction of future CV events and death.