Sarah Janssens

Hyperosmotic stress induces cell cycle arrest in retinal pigmented epithelial cells

Osmotic changes occur in many tissues and profoundly influence cell function. Herein, we investigated the effect of hyperosmotic stress on retinal pigmented epithelial (RPE) cells using a microarray approach. Upon 4-h exposure to 100 mM NaCl or 200 mM sucrose, 79 genes were downregulated and 72 upregulated. Three gene ontology categories were significantly modulated: cell proliferation, transcription from RNA polymerase II promoter and response to abiotic stimulus. Fluorescent-activated cell sorting analysis further demonstrated that owing to hyperosmotic stimulation for 24 h, cell count and cell proliferation, as well as the percentage of cells in G0/G1 and S phases were significantly decreased, whereas the percentage of cells in G2/M phases increased, and apoptosis and necrosis remained unaffected. Accordingly, hyperosmotic conditions induced a decrease of cyclin B1 and D1 expression, and an activation of the p38 mitogen-activated protein kinase. In conclusion, our results demonstrate that hypertonic conditions profoundly affect RPE cell gene transcription regulating cell proliferation by downregulation cyclin D1 and cyclin B1 protein expression.

Clinical Outcome of Hypertensive Uveitis

Purpose. To review the clinical outcome of patients with hypertensive uveitis. Methods. Retrospective review of uveitis patients with elevated intraocular pressure (IOP) > 25 mmHg and >1-year follow-up. Data are uveitis type, etiology, viral (VU) and nonviral uveitis (NVU), IOP, and medical and/or surgical treatment. Results. In 61 patients, IOP values are first 32.9 mmHg (SD: 9.0), highest 36.6 mmHg (SD: 9.9), 3 months after the first episode 19.54 mmHg (SD: 9.16), and end of follow-up 15.5 mmHg (SD: 6.24). Patients with VU (n = 25) were older (50.6 y/35.7 y, p = 0.014) and had more unilateral disease (100%/72.22%  p = 0.004) than those with NVU (n = 36). Thirty patients (49.2%) had an elevated IOP before topical corticosteroid treatment. Patients with viral uveitis might have higher first elevated IOP (36.0/27.5 mmHg, p = 0,008) and maximal IOP (40.28/34.06 mmHg, p = 0.0148) but this was not significant when limited to the measurements before the use of topical corticosteroids (p = 0.260 and 0.160). Glaucoma occurred in 15 patients (24.59%) and was suspected in 11 (18.03%) without difference in viral and nonviral groups (p = 0.774). Conclusion. Patients with VU were older and had more unilateral hypertensive uveitis. Glaucoma frequently complicates hypertensive uveitis. Half of the patients had an elevated IOP before topical corticosteroid treatment.

Osmotic stress decreases aquaporin-4 expression in the human retinal pigment epithelial cell line, ARPE-19

The regulation of water movement is of utmost importance for normal retinal function. Under physiological conditions, water is transported, dependent on the osmotic gradient, through the retinal pigment epithelial cell layer from the subretinal space to the choroid. The osmotic gradient has been found to be modified in eye diseases, thus leading to water accumulation in the subretinal space and the sensory retina, and subsequently contributing to the formation of macular oedema. Understanding the regulation of aquaporin expression is therefore crucial. In this study, we investigated the effects of hyperosmolarity on aquaporin-4 (AQP4) protein expression in the human retinal pigment epithelial cell line, ARPE‑19. AQP4 expression was examined by PCR, western blot analysis and immunofluorescence. Ubiquitinylation was examined by immunoprecipitation. The results revealed that hyperosmotic stress rapidly decreased AQP4 expression in the ARPE-19 cells. The effect remained unmodified by lysosomal or mitogen-activated protein kinase inhibitors, but was reversed by proteasome inhibitors. However, no ubiquitinylation of AQP4 was detected. Our results suggest that hyperosmotic stress markedly reduces AQP4 expression possibly through a proteasome ubiquitinylation-independent pathway. This may represent an adaptation to hyperosmotic stress. The results presented in this study contribute to our understanding of the formation of macular oedema.

Bilateral retinal ischemic vasculopathy in a pregnant patient.

PURPOSE To present the case of a young Turkish pregnant patient with bilateral, sight-threatening retinal ischemic vasculopathy and systemic signs suggestive of Behçet disease (oral ulceration, arthritis, and pseudofolliculitis). METHODS Case report. RESULTS Multiple areas of superficial, retinal white lesions and few hemorrhages related to occlusions of small retinal vessels were observed at presentation in the macular zone of both eyes. There was gradual improvement of retinal lesions after the administration of corticosteroids and immunosuppressive treatment. CONCLUSION We report the case of a young pregnant patient with bilateral, sight-threatening retinal ischemic vasculopathy and systemic signs of Behçet disease. Although the systemic signs were highly suggestive of Behçet disease, the ocular presentation was unusual for this multisystemic inflammatory disorder. The differential diagnosis included a number of causes of ischemic retinal vasculopathy, such as systemic vasculitis, antiphospholipid syndrome, Susac syndrome, Purtscher-like retinopathy, and a new variant of acute macular neuroretinopathy (paracentral, acute middle maculopathy), which are further discussed.

Distribution of uveitis in a Belgian university referral center for ocular inflammation

Purpose : To study the clinical characteristics of patients with uveitis seen in our center.