Masahiro Minami

Effects of angiotensin II on the pericyte‐containing microvasculature of the rat retina

The aim of this study was to identify the mechanisms by which angiotensin II alters the physiology of the pericyte‐containing microvasculature of the retina. Despite evidence that this vasoactive signal regulates capillary perfusion by inducing abluminal pericytes to contract and thereby microvascular lumens to constrict, little is known about the events linking angiotensin exposure with pericyte contraction. Here, using microvessels freshly isolated from the adult rat retina, we monitored pericyte currents via perforated‐patch pipettes, measured pericyte calcium levels with fura‐2 and visualized pericyte contractions and lumen constrictions by time‐lapse photography. We found that angiotensin activates nonspecific cation (NSC) and calcium‐activated chloride channels; the opening of these channels induces a depolarization that is sufficient to activate the voltage‐dependent calcium channels (VDCCs) expressed in the retinal microvasculature. Associated with these changes in ion channel activity, intracellular calcium levels rise, pericytes contract and microvascular lumens narrow. Our experiments revealed that an influx of calcium through the NSC channels is an essential step linking the activation of AT1 angiotensin receptors with pericyte contraction. Although not required in order for angiotensin to induce pericytes to contract, calcium entry via VDCCs serves to enhance the contractile response of these cells. In addition to activating nonspecific cation, calcium‐activated chloride and voltage‐dependent calcium channels, angiotensin II also causes the functional uncoupling of pericytes from their microvascular neighbours. This inhibition of gap junction‐mediated intercellular communication suggests a previously unappreciated complexity in the spatiotemporal dynamics of the microvascular response to angiotensin II.

Electrotonic transmission within pericyte-containing retinal microvessels

Objective: Little is known about the electrotonic architecture of the pericyte‐containing retinal microvasculature. Here, the authors focus on the cell‐to‐cell transmission of hyperpolarization, which can induce abluminal pericytes to relax and lumens to dilate.

Diabetes-induced inhibition of voltage-dependent calcium channels in the retinal microvasculature: role of spermine.

PURPOSE Although decentralized control of blood flow is particularly important in the retina, knowledge of the functional organization of the retinal microvasculature is limited. Here, the authors characterized the distribution and regulation of L-type voltage-dependent calcium channels (VDCCs) within the most decentralized operational complex of the retinal vasculature--the feeder vessel/capillary unit--which consists of a capillary network plus the vessel linking it with a myocyte-encircled arteriole. METHODS Perforated-patch recordings, calcium-imaging, and time-lapse photography were used to assess VDCC-dependent changes in ionic currents, intracellular calcium, abluminal cell contractility, and lumen diameter, in microvascular complexes freshly isolated from the rat retina. RESULTS Topographical heterogeneity was found in the distribution of functional VDCCs; VDCC activity was markedly greater in feeder vessels than in capillaries. Experiments showed that this topographical distribution occurs, in large part, because of the inhibition of capillary VDCCs by a mechanism dependent on the endogenous polyamine spermine. An operational consequence of functional VDCCs predominantly located in the feeder vessels is that voltage-driven vasomotor responses are generated chiefly in this portion of the feeder vessel/capillary unit. However, early in the course of diabetes, this ability to generate voltage-driven vasomotor responses becomes profoundly impaired because of the inhibition of feeder vessel VDCCs by a spermine-dependent mechanism. CONCLUSIONS The regulation of VDCCs by endogenous spermine not only plays a critical role in establishing the physiological organization of the feeder vessel/capillary unit, but also may contribute to dysfunction of this decentralized operational unit in the diabetic retina.

Progression of nuclear sclerosis based on changes in refractive values after lens-sparing vitrectomy in proliferative diabetic retinopathy

Background Nuclear sclerosis (NS) based on the Emery–Little classification and refractive values after lens-sparing vitrectomy was compared between proliferative diabetic retinopathy (DR) patients and nondiabetic patients. Methods Progression of NS based on the Emery–Little classification and changes in refractive values were compared between 13 proliferative DR patients (14 eyes, DR group) and 14 nondiabetic patients (14 eyes, non-DR group) who underwent lens-sparing vitrectomy. All patients revealed grade I NS based on the Emery–Little classification. Mean patient age and refractive value just after surgery were 56.07 years and −0.33 diopters (D) in the DR group, and 57.06 years and −0.96 D in the non-DR group. Results The Emery–Little classification in the DR group at 6 and 24 months postoperative were grade I (13 eyes)/grade II (one eye) and grade I (eleven eyes)/grade II (three eyes), respectively. Mean refractive values in the DR group at 6, 12, and 24 months postoperative were +0.28 D, +0.27 D, and +0.37 D, respectively. The Emery–Little classification in the non-DR group at 6 and 24 months (or preoperative for patients undergoing cataract surgery) were grade I (five eyes)/grade II (eight eyes) and grade I (zero eyes)/grade II (eight eyes)/grade III (five eyes), respectively. The mean refractive value in the non-DR group at 6 months postoperative was −3.20 D. All eyes exhibited myopic changes and progression of NS. Conclusion The findings of this study show that the progression of NS postvitrectomy is mild, even for DR patients 50 years of age or older, thus suggesting the need to reconsider the indications for simultaneous cataract surgery with vitrectomy.

Senior-loken syndrome complicated with severe coats disease-like exudative retinopathy.

BACKGROUND Senior-Loken syndrome is a rare disorder that combines juvenile nephronophthisis with retinitis pigmentosa. METHODS Case report. RESULTS A 9-year-old Japanese girl diagnosed with Senior-Loken syndrome subsequently developed severe Coats disease-like exudative retinopathy. Although retinal coagulation, pars plana lensectomy, and vitrectomy were performed, she lost light perception in both eyes. CONCLUSION Faulty vascular morphogenesis and its dysfunction might contribute to the development of Coats disease-like exudative retinopathy in Senior-Loken syndrome.