Membrane-anchored intracellular insulin receptor or insulin-like growth factor-1 receptor elicits ligand-independent downstream signaling.

Neurodegenerative diseases including glaucoma affect insulin signaling, and insulin treatment has been shown to reverse the neurodegenerative loss of dendritic complexity in retinal ganglion cells. Therefore, strategies for enhancing or maintaining insulin signaling are worth pursuing to establish new therapies for these diseases. In the present study, we generated constitutively active insulin receptor (F-iIR) and insulin-like growth factor-1 receptor (F-iIGF1R) using a system that forces membrane localization of the intracellular domains of these receptors by farnesylation. Immunohistochemistry and Western blot analysis revealed that F-iIR and F-iIGF1R caused the activation of ERK and AKT in the absence of ligands in vitro. Our results suggest that in vivo effects of F-iIR and F-iIGF1R on the progression of neurodegenerative diseases should be investigated in the future.

Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury.

PURPOSE: To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve. METHODS: Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina. RESULTS: Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1ß and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF). CONCLUSIONS: Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.

Case Report: Improved Choroidal Circulation in a Patient with Unilateral Acute Idiopathic Maculopathy.

SIGNIFICANCE: Unilateral acute idiopathic maculopathy is a rare retinochoroidal disorder, the cause of which is unknown. Multimodal retinal imaging obtained in this case suggests that the cause of unilateral acute idiopathic maculopathy is impaired choroidal circulation. PURPOSE: This study aimed to report a patient with unilateral acute idiopathic maculopathy who showed improvement of choroidal circulation over time in optical coherence tomography angiography images. CASE REPORT: A 33-year-old woman with a prodromal flu-like illness noticed a sudden central visual field abnormality in the right eye. Five days after the onset, best-corrected visual acuity was 0.15 in the right eye. Fundus photography showed a yellowish lesion at the macula in the right eye. Optical coherence tomography showed a blurred ellipsoid zone and a thickened retinal pigment epithelium at the fovea and a disrupted/blurred ellipsoid zone and retinal pigment epithelium at the parafovea. Optical coherence tomography angiography segmentation of the choriocapillaris revealed a hypointense region at the fovea with a hyperintense region surrounding it. One week after the onset, best-corrected visual acuity was improved from 0.15 to 2.0 in the right eye. Furthermore, the yellowish macula lesion shrank, and the outer retinal layers showed improvement in optical coherence tomography. Optical coherence tomography angiography showed reduction of the hypointense region and enlargement of the hyperintense region. Approximately 1 year after the onset, the yellowish lesion was faded. Optical coherence tomography revealed an almost normal ellipsoid zone but a thickened interdigitation zone. Optical coherence tomography angiography also revealed an apparent hyperintense instead of the hypointense region and increased choroidal blood flow. CONCLUSIONS: The current patient showed a gradual recovery of choroidal circulation and outer retinal layer morphology 1 year after the onset of unilateral acute idiopathic maculopathy. Optical coherence tomography angiography findings indicated that the primary cause of unilateral acute idiopathic maculopathy was impaired choroidal circulation, and choroidal vessels improved morphologically over the disease course.

Seasonal fluctuation in intraocular pressure and its associated factors in primary open-angle glaucoma.

BACKGROUND/OBJECTIVES: To evaluate seasonal fluctuations in intraocular pressure (IOP) in primary open-angle glaucoma (POAG) and its associated factors. SUBJECTS/METHODS: POAG patients treated only with glaucoma eye drops were enroled. Winter and summer IOPs were evaluated. The Seasonal fluctuation rate of IOP was defined as follows: (mean winter IOP-mean summer IOP)/mean IOP in all seasons. Multiple linear regression analysis was used to explore factors associated with the seasonal IOP fluctuation rate including: age, gender, family history of glaucoma, type of glaucoma, number of eye drops, type of eye drops, mean deviation (MD) value, MD slope, disc haemorrhage, central corneal thickness and spherical equivalent. RESULTS: Winter IOP was higher than summer IOP in 204 POAG eyes of 204 patients, including 162 eyes with normal tension glaucoma (NTG) (13.2 ± 2.7 vs. 12.0 ± 2.3 mmHg, P < 0.001). The mean age and follow-up duration were 63.3 ± 11.4 years and 140.0 ± 66.9 months. Initial MD and MD slope were -2.1 ± 3.4 dB and -0.07 ± 0.50 dB/year, respectively. POAG was positively associated with the rate of seasonal IOP fluctuations compared to NTG (ß = 5.29, P = 0.013). Family history, and timolol and carteolol use were also factors associated with the IOP fluctuation rate (ß = -6.27, P = 0.007; ß = 4.94, P = 0.030; and ß = 4.51, P = 0.042, respectively). CONCLUSIONS: We confirmed seasonal IOP fluctuations in POAG. Type of glaucoma, family history of glaucoma, and ß-blocker use might influence IOP fluctuations.