Diabetic retinopathy is a debilitating microvascular complication of diabetes mellitus. A rich literature describes the breakdown of retinal endothelial cells and the inner blood-retinal barrier, but the effects of diabetes on the retinal pigment epithelium (RPE) has received much less attention. RPE lies between the choroid and neurosensory retina to form the outer blood-retinal barrier. RPE's specialized and dynamic barrier functions are crucial for maintaining retinal health. RPE barrier functions include a collection of interrelated structures and activities that regulate the transepithelial movement of solutes, including: diffusion through the paracellular spaces, facilitated diffusion through the cells, active transport, receptor-mediated and bulk phase transcytosis, and metabolic processing of solutes in transit. In the later stages of diabetic retinopathy, the tight junctions that regulate the paracellular space begin to disassemble, but there are earlier effects on the other aspects of RPE barrier function, particularly active transport and metabolic processing. With advanced understanding of RPE-specific barrier functions, and more in vivo-like culture models, the time is ripe for revisiting experiments in the literature to resolve controversies and extend our understanding of how diabetes affects the outer blood-retinal barrier.
Investigators, scientists, and physicians continue to develop new methods of intraocular lens (IOL) calculation to improve the refractive accuracy after cataract surgery. To gain more accurate prediction of IOL power, vergence lens formulas have incorporated additional biometric variables, such as anterior chamber depth, lens thickness, white-to-white measurement, and even age in some algorithms. Newer formulas diverge from their classic regression and vergence-based predecessors and increasingly utilize techniques such as exact ray-tracing data, more modern regression models, and artificial intelligence. This review provides an update on recent literature comparing the commonly used third- and fourth-generation IOL formulas with newer generation formulas. Refractive outcomes with newer formulas are increasingly more and more accurate, so it is important for ophthalmologists to be aware of the various options for choosing IOL power. Historically, refractive outcomes have been especially unpredictable in patients with unusual biometry, corneal ectasia, a history of refractive surgery, and in pediatric patients. Refractive outcomes in these patient populations are improving. Improved biometry technology is also allowing for improved refractive outcomes and surgery planning convenience with the availability of newer formulas on various biometry platforms. It is crucial for surgeons to understand and utilize the most accurate formulas for their patients to provide the highest quality of care.
Chronic myelogenous leukemia patients treated with tyrosine kinase inhibitor, Imatinib, were shown to have increased serum levels of C-peptide. Imatinib specifically inhibits the tyrosine kinase, c-Abl. However, the mechanism of how Imatinib treatment can lead to increased insulin level is unclear. Specifically, there is little investigation into whether Imatinib directly affects β cells to promote insulin production. In this study, we showed that Imatinib significantly induced insulin expression in both glucose-stimulated and resting β cells. In line with this finding, c-Abl knockdown by siRNA and overexpression of c-Abl markedly enhanced and inhibited insulin expression in β cells, respectively. Unexpectedly, high concentrations of glucose significantly induced c-Abl expression, suggesting c-Abl may play a role in balancing insulin production during glucose stimulation. Further studies demonstrated that c-Abl inhibition did not affect the major insulin gene transcription factor, pancreatic and duodenal homeobox-1 (PDX-1) expression. Of interest, inhibition of c-Abl enhanced NKx2.2 and overexpression of c-Abl in β cells markedly down-regulated NKx2.2, which is a positive regulator for insulin gene expression. Additionally, we found that c-Abl inhibition significantly enhanced the expression of glucose transporter GLUT2 on β cells. Our study demonstrates a previously unrecognized mechanism that controls insulin expression through c-Abl-regulated NKx2.2 and GLUT2. Therapeutic targeting β cell c-Abl could be employed in the treatment of diabetes or β cell tumor, insulinoma.
The feasibility of using a nonmydriatic camera to screen children as young as 2 years for changes related to diabetic eye disease was demonstrated. Nonmydriatic imaging may supplement standard dilated clinical ophthalmology examinations for select patient populations.
PURPOSE. Many studies have demonstrated the ability of the retinal pigment epithelium (RPE) to foster the maturation of the developing retina. Few studies have examined the reciprocal effects of developing retina on the RPE. METHODS. RPE isolated from human fetal RPE or differentiated from human stem cells was cultured on Transwell filter inserts. Retinal progenitor cells (RPCs) were differentiated from human stem cells and cultured on a planar scaffold composed of gelatin, chondroitin sulfate, hyaluronic acid, and laminin-521. Cultures were analyzed by quantitative RT-PCR, immunofluorescence, immunoblotting, and transepithelial electrical resistance (TER). RESULTS. RPCs initially differentiated into several retina-like cell types that segregated from one another and formed loosely organized layers or zones. With time, the presumptive photoreceptor and ganglion cell layers persisted, but the intervening zone became dominated by cells that expressed glial markers with no evidence of bipolar cells or interneurons. Co-culture of this underdeveloped retinoid with the RPE resulted in a thickened layer of recoverin-positive cells but did not prevent the loss of interneuron markers in the intervening zone. Although photoreceptor inner and outer segments were not observed, immunoblots revealed that co-culture increased expression of rhodopsin and red/green opsin. Co-culture of the RPE with this underdeveloped retinal culture increased the TER of the RPE and the expression of RPE signature genes. CONCLUSIONS. These studies indicated that an immature neurosensory retina can foster maturation of the RPE; however, the ability of RPE alone to foster maturation of the neurosensory retina is limited.
The complementary use of noninvasive imaging modalities such as fundus autofluorescence, red/green/blue separation, B-scan, and optical coherence tomography is important in confirming the diagnosis of ONHD in pediatric patients. They allow us to rule out more serious conditions and avoid unnecessary, costly, and invasive investigative procedures, relieving young patients and their families of potential financial and emotional burdens.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.