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Background/aimsTo study the multimodal imaging findings of a large series of eyes with cilioretinal artery obstruction (CILRAO) and describe the systemic associations.MethodsMulticentre, retrospective chart review from 12 different retina clinics worldwide of eyes with CILRAO, defined as acute retinal whitening in the distribution of the cilioretinal artery, were identified. The clinical, systemic information and multimodal retinal imaging findings were collected and analysed.ResultsA total of 53 eyes of 53 patients with CILRAO were included in the study. In 100% of eyes, fundus photography illustrated deep retinal whitening corresponding to the course of the cilioretinal artery. Twenty-eight patients (52.8%) presented with isolated CILRAO (baseline best-corrected visual acuity (BCVA) 20/50, final BCVA 20/25) associated with nocturnal hypotension, 23 patients (43.4%) with CILRAO secondary to central retinal vein occlusion (CRVO) (baseline BCVA 20/40, final BCVA 20/20) and two patients with CILRAO due to biopsy-proven giant cell arteritis (GCA) (baseline BCVA 20/175, final BCVA 20/75). With spectral domain optical coherence tomography (SD-OCT), a hyper-reflective band involving the inner nuclear layer (ie, paracentral acute middle maculopathy or PAMM) was noted in 51 eyes (28/28 eyes with isolated CILRAO and 23/23 eyes with CILRAO+CRVO) corresponding to the retinal whitening. In the two eyes with CILRAO+GCA, SD-OCT illustrated hyper-reflective ischaemia of both the middle and inner retina.ConclusionsIsolated CILRAO and CILRAO secondary to CRVO are the result of hypoperfusion or insufficiency, rather than occlusion, of the cilioretinal artery and are associated with PAMM or selective infarction of the the inner nuclear layer. With GCA, there is complete occlusion of the cilioretinal artery producing ischaemia involving both the middle and inner retina associated with worse visual outcomes.

No author has a financial or proprietary interest in any material or method mentioned.

Differentiation of hematopoietic cells is known to be accompanied by profound changes in acetylcholinesterase (AChE) enzyme activity, yet the basic mechanisms underlying this developmental regulation remain unknown. We initiated a series of experiments to examine the molecular mechanisms involved in regulating AChE expression during hematopoiesis. Differentiation of murine erythroleukemia (MEL) cells using dimethyl sulfoxide resulted in a 5-and 10-fold increase in intracellular and secreted AChE enzyme activity, respectively. Interestingly, these increases resulted from a preferential induction of the globular molecular form G 1 and a slight increase in G 4 instead of an increase in the levels of the G 2 membrane-bound form, a molecular form expressed in mature erythrocytes. Concomitantly, expression of the two predominant AChE transcripts (R and T, for read-through and tail, respectively) in MEL cells was induced to a similar extent with differentiation. Nuclear run-on assays performed with nuclei isolated from induced versus uninduced MEL cells revealed that in contrast to the large increases seen in the transcription of the ␤-globin gene, the transcriptional activity of the AChE gene remained largely unaffected after differentiation. Determination of the half-lives of the R and T transcripts demonstrated that they both exhibited an increase in stability in induced MEL cells. Taken together, results from these studies indicate that posttranscriptional regulatory mechanisms account for the increased expression of AChE in differentiated hematopoietic cells.

Activation of glucagon-like peptide (GLP)-1 receptor signaling promotes glucose lowering via multiple mechanisms, including regulation of food intake, glucose-dependent insulin secretion, and stimulation of ␤-cell mass. As GLP-1 exhibits a short t1 ⁄2 in vivo, the biological consequences of prolonged GLP-1 receptor signaling remains unclear. To address this question, we have now generated metallothionein promoter-preproexendin (MT-Ex) transgenic mice. MT-Ex mice process preproexendin correctly, as is made evident by detection of circulating plasma exendin-4 immunoreactivity using high pressure liquid chromatography and an exendin-4-specific radioimmunoassay. Despite elevated levels of exendin-4, fasting plasma glucose and glucose clearance following oral and intraperitoneal glucose tolerance tests are normal in MT-Ex mice. Induction of transgene expression significantly reduced glycemic excursion during both oral and intraperitoneal glucose tolerance tests (p < 0.05) and increased levels of glucose-stimulated insulin following oral glucose administration (p < 0.05). Despite evidence that exendin-4 may induce ␤-cell proliferation, ␤-cell mass and islet histology were normal in MT-Ex mice. MT-Ex mice exhibited no differences in basal food intake or body weight; however, induction of exendin-4 expression was associated with reduced short term food ingestion (p < 0.05). In contrast, short term water intake was significantly reduced in the absence of zinc in fluid-restricted MT-Ex mice (p < 0.05). These findings illustrate that sustained elevation of circulating exendin-4 is not invariably associated with changes in glucose homeostasis, increased ␤-cell mass, or reduction in food intake in mice in vivo.Glucagon-like peptide-1 (GLP-1), 1 a product of the proglucagon gene, is released from gut endocrine cells and potentiates glucose-dependent insulin secretion (1). GLP-1 also regulates gastric emptying, food intake, glucagon secretion, and islet proliferation and hence is currently under investigation as a therapeutic agent for the treatment of diabetes (1). However, a significant limitation to potential GLP-1 therapy in diabetic subjects is the short biological half-life of this peptide (2-4), limiting its ability to control blood glucose for an extended period of time. These considerations have prompted investigation of strategies designed to prolong the duration of GLP-1 action in vivo (5, 6). Exendin-4, a peptide structurally related to but distinct from GLP-1 (7) was originally purified from the venom of a Heloderma suspectum lizard (8, 9). Subsequent characterization of exendin-4 activity demonstrated that the lizard peptide was a potent agonist for the mammalian glucagon-like peptide-1 receptor (GLP-1R) (8 -11). Exendin-4 exhibits a much longer in vivo half-life and prolonged duration of action (11), rendering it more potent for continuous stimulation of GLP-1 receptor signaling and sustained improvement in glucose homeostasis in vivo. Despite the structural homology of lizard exendin-4 and mammalian GLP-1, a ma...

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