Endogenous adenosine has already been shown to inhibit transmitter release from the rod synapse by suppressing Ca 2+ influx through voltage-gated Ca 2+ channels. However, it is not clear how adenosine modulates the cone synapse. Cone photoreceptors, like rod photoreceptors, also possess L-type Ca 2+ channels that regulate the release of L-glutamate. To assess the impact of adenosine on Ca 2+ influx though voltage-gated Ca 2+ channels in cone terminals, whole-cell perforated-patch clamp recording and Ca 2+ imaging with fluo-4 were used on isolated cones and salamander retinal slices. Synaptic markers (VAMP and piccolo) and activity-dependent dye labeling revealed that tiger salamander cone terminals contain a broad, vesicle-filled cytoplasmic extension at the base of the somatic compartment, which is unlike rod terminals that contain one or more thin axons, each terminating in a large bulbous synaptic terminal. The spatiotemporal Ca 2+ responses of the cone terminals do not differ significantly from the Ca 2+ responses of the soma or inner segment like that observed in rods. Whole-cell recording of cone I Ca and Ca 2+ imaging of synaptic terminals in cones demonstrate that adenosine inhibited both I Ca and the depolarization-evoked Ca 2+ increase in cone terminals in a dose-dependent manner from 1 to 50 μM, with an EC 50 of 15.6 μM. These results indicate that, as in rods, adenosine's ability to suppress voltage-dependent Ca 2+ channels at the cone synapse will limit the amount of L-glutamate released. Therefore, adenosine has an inhibitory effect on L-glutamate release at the first synapse, which likely favors elevated adenosine levels in the dark or during dark-adapted conditions. Keywords FM 4-64; Synaptored-C2; fluo-4; VAMP; piccolo In the retina, adenosine has been shown to be under tight regulation by light and dark conditions (Ribelaya and Mangel, 2005), and it is the changing conditions of illumination that influence adenosine levels (Blazanski and Perez, 1991;Paes de Carvalho, 2002;Sun et al., 2002;Stella et al., 2003; Ribelaya and Mangel, 2005), making adenosine concentrations higher in the dark and lower in the light. Adenosine can also inhibit Ca 2+ channels and
This cross-sectional study aimed to evaluate adherence rates and identify barriers to receiving follow-up eye care in participants diagnosed with significant non-glaucomatous eye pathology in the Philadelphia Glaucoma Detection and Treatment Project. This community-based project aimed to improve detection, management, treatment, and follow-up eye care of individuals at high risk for glaucoma in community-based settings. Participants throughout Philadelphia, Pennsylvania, USA were enrolled. After a comprehensive eye examination, follow-up recommendations were given to each participant. A telephone survey was administered to individuals diagnosed with non-glaucomatous ocular pathology 3 months after initial eye examination to assess rates of follow-up and to evaluate potential barriers to follow-up. Of the 1649 participants enrolled in this project, 249 (15 %) were diagnosed with significant non-glaucomatous ocular pathology requiring follow-up care. There were 143 (57 %) who responded to the telephone survey. Respondents had a median age of 72 years, and were predominately female (69 %) and African-American (64 %). Of the respondents, 36 (25 %) attended a follow-up appointment. Participants who did not remember the results of their examinations, did not remember their recommendations, and had not seen an eye doctor within the past year were less likely to make a follow-up appointment (P = 0.04, 0.001 and 0.005, respectively). The Philadelphia Glaucoma Detection and Treatment Program was able to detect a significant amount of non-glaucomatous ocular pathology requiring follow-up care. Actual follow-up rates were sub-optimal. Further research is needed to determine interventions to overcome barriers and increase adherence with follow-up recommendations.
PurposeTo investigate the clinical outcomes of tube shunt coverage using sterile gamma-irradiated cornea allograft.Patients and methodsThe Wills Eye Hospital Glaucoma Research Center retrospectively reviewed the medical records of 165 patients who underwent glaucoma tube shunt procedures using sterile gamma-irradiated cornea allograft (VisionGraft) between December 2012 and November 2013. Demographic characteristics, type of tube shunt, and position were noted. Complications were recorded at 1 day; 1 week; 1, 3, 6, and 12 months; and on the final postoperative visit.ResultsOne hundred and sixty-nine eyes of 165 patients were included. The mean follow-up time was 4.8±3.5 (ranging from 1 to 16) months. There was no evidence of immunological reaction, infection, or exposure in 166 eyes (98.2%). Three eyes (1.8%) experienced graft or tube exposure within the first 3 postoperative months. Two of the cases had underlying diseases: bullous pemphigoid and chronic allergic conjunctivitis.ConclusionCoverage of tube shunts using gamma-irradiated cornea allograft had a low exposure rate and was well tolerated. The graft can be stored long term at room temperature and has an excellent postoperative cosmetic appearance.
In the retina, adenosine is released in the dark and has been shown to inhibit Ca 2+ influx through voltage-gated Ca 2+ channels in cones. Therefore, we tested whether adenosine can inhibit exocytosis from isolated cone photoreceptors. Simultaneous measurements of membrane exocytosis and Ca 2+ were made from cones using the activity-dependent dye, Synaptored-C2, and the Ca 2+ indicator dye, Fluo-4. Adenosine suppressed exocytosis in cones, indicating that transmitter release is also reduced from cone terminals, and further supports an inhibitory mechanism for modulating transmitter release onto second-order neurons. Furthermore, this raises the possibility that adenosine might be neuroprotective for photoreceptors and second-order neurons by suppressing Ca 2+ levels in cones and reducing exocytosis of L-glutamate, respectively.
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