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The essential task of the circulatory system is to match blood flow to local metabolic demand. However, much remains to be learned about this process. To better understand how local perfusion is regulated, we focused on the functional organization of the retinal microvasculature, which is particularly well adapted for the local control of perfusion. Here, we assessed the distribution and regulation of functional KATP channels whose activation mediates the hyperpolarization induced by adenosine. Using microvascular complexes freshly isolated from the rat retina, we found a topographical heterogeneity in the distribution of functional KATP channels; capillaries generate most of the KATP current. The initiation of KATP-induced responses in the capillaries supports the concept that the regulation of retinal perfusion is highly decentralized. Additional study revealed that microvascular KATP channels are redox sensitive, with oxidants increasing their activity. Furthermore, the oxidant-mediated activation of these channels is driven by the polyamine spermine, whose catabolism produces oxidants. In addition, our observation that spermine-dependent oxidation occurs predominately in the capillaries accounts for why they generate most of the KATP current detected in retinal microvascular complexes. Here, we also analysed retinal microvessels of streptozotocin-injected rats. We found that soon after the onset of diabetes, an increase in spermine-dependent oxidation at proximal microvascular sites boosts their KATP current and thereby virtually eliminates the topographical heterogeneity of functional KATP channels. We conclude that spermine-dependent oxidation is a previously unrecognized mechanism by which this polyamine modulates ion channels; in addition to a physiological role, spermine-dependent oxidation may also contribute to microvascular dysfunction in the diabetic retina. [ABSTRACT FROM AUTHOR]

This case report describes a case of Alagille syndrome with developing intraocular lens subluxation and rhegmatogenous retinal detachment 4 years after cataract surgery. A 15-year-old female patient with Alagille syndrome-associated cataracts in both eyes underwent phacoemulsification aspiration and intraocular lens implantation. Four years postoperative, intraocular lens subluxation developed in her left eye. For treatment, extraction of the dislocated intraocular lens, anterior vitrectomy, and intraocular lens fixation was performed. Three weeks later, the patient developed rhegmatogenous retinal detachment, which was well-treated by pars plana vitrectomy. Cataract surgery needs to be performed carefully in patients with Alagille syndrome due to the weakness of the zonule of Zinn. Careful postoperative observation is necessary for patients with Alagille syndrome who have undergone intraocular surgery in order to facilitate early detection of a possible rhegmatogenous retinal detachment. [ABSTRACT FROM AUTHOR]

P2X 7 receptor/channels in the retinal microvasculature not only regulate vasomotor activity, but can also trigger cells in the capillaries to die. While it is known that this purinergic vasotoxicity is dependent on the transmembrane pores that form during P2X 7 activation, events linking pore formation with cell death remain uncertain. To better understand this pathophysiological process, we used YO-PRO-1 uptake, dichlorofluorescein fluorescence, perforated-patch recordings, fura-2 imaging and trypan blue dye exclusion to assess the effects of the P2X 7 agonist, benzoylbenzoyl-ATP (BzATP), on pore formation, oxidant production, ion channel activation, [Ca 2+ ] i and cell viability. Experiments demonstrated that exposure of retinal microvessels to BzATP increases capillary cell oxidants via a mechanism dependent on pore formation and the enzyme, NADPH oxidase. Indicative that oxidation plays a key role in purinergic vasotoxicity, an inhibitor of this enzyme completely prevented BzATP-induced death. We further discovered that vasotoxicity was boosted 4-fold by a pathway involving the oxidation-driven activation of hyperpolarizing K ATP channels and the resulting increase in calcium influx. Our findings revealed that the previously unappreciated pore/oxidant/K ATP channel/Ca 2+ pathway accounts for 75% of the capillary cell death triggered by sustained activation of P2X 7 receptor/channels. Elucidation of this pathway is of potential therapeutic importance since purinergic vasotoxicity may play a role in sight-threatening disorders such as diabetic retinopathy., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.