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A novel serine protease inhibitor as potential treatment for dry eye syndrome and ocular inflammation.

ABSTRACT: Dry eye syndrome (DES), a multifactorial disorder which leads to ocular discomfort, visual disturbance and tear film instability, has a rising prevalence and limited treatment options. In this study, a newly developed trypsin-like serine protease inhibitor (UAMC-00050) in a tear drop formulation was evaluated to treat ocular inflammation. A surgical animal model of dry eye was employed to investigate the potential of UAMC-00050 on dry eye pathology. Animals treated with UAMC-00050 displayed a significant reduction in ocular surface damage after evaluation with sodium fluorescein, compared to untreated, vehicle treated and cyclosporine-treated animals. The concentrations of IL-1? and TNF-? were also significantly reduced in tear fluid from UAMC-00050-treated rats. Additionally, inflammatory cell infiltration in the palpebral conjunctiva (CD3 and CD45), was substantially reduced. An accumulation of pro-MMP-9 and a decrease in active MMP-9 were found in tear fluid from animals treated with UAMC-00050, suggesting that trypsin-like serine proteases play a role in activating MMP-9 in ocular inflammation in this animal model. Comparative qRT-PCR analyses on ocular tissue indicated the upregulation of tryptase, urokinase plasminogen activator receptor (uPAR) and protease-activated receptor 2 (PAR2). The developed UAMC-00050 formulation was stable up to 6 months at room temperature in the absence of light, non-irritating and sterile with compatible pH and osmolarity. These results provide a proof-of-concept for the in vivo modifying potential of UAMC-00050 on dry eye pathology and suggest a central role of trypsin-like serine proteases and PAR2 in dry eye derived ocular inflammation.

SUBMITTER: Joossen C

PROVIDER: S-EPMC7560718 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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A novel serine protease inhibitor as potential treatment for dry eye syndrome and ocular inflammation.

Joossen Cedric C Baán Adrienn A Moreno-Cinos Carlos C Joossens Jurgen J Cools Nathalie N Lanckacker Ellen E Moons Lieve L Lemmens Kim K Lambeir Anne-Marie AM Fransen Erik E Delputte Peter P Caljon Guy G Van Der Veken Pieter P Maes Louis L De Meester Ingrid I Kiekens Filip F Augustyns Koen K Cos Paul P

Scientific reports 20201014 1

Dry eye syndrome (DES), a multifactorial disorder which leads to ocular discomfort, visual disturbance and tear film instability, has a rising prevalence and limited treatment options. In this study, a newly developed trypsin-like serine protease inhibitor (UAMC-00050) in a tear drop formulation was evaluated to treat ocular inflammation. A surgical animal model of dry eye was employed to investigate the potential of UAMC-00050 on dry eye pathology. Animals treated with UAMC-00050 displayed a si ...[more]

PMID: 33057006

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Project description:ObjectiveTo find preoperative screening criteria for dry eye syndrome (DES) that present after successful endoscopic dacryocystorhinostomy (EDCR).MethodsWe retrospectively analyzed medical records of 110 patients who underwent EDCR for nasolacrimal duct obstruction. DES diagnostic criteria were defined as tear break-up time (TBUT) less than 10 seconds, and ocular surface disease index (OSDI) score greater than 13 points. After EDCR, patients were divided into DES group and control group according to the DES diagnostic criteria. Preoperative OSDI score alone or in combination of preoperative TBUT and OSDI score were used to find screening criteria, which could discriminate the two groups preoperatively with a high positive predictive value (PPV). Criteria A was set same as the diagnostic criteria of DES, and Criteria B and C were set to improve PPV by increasing specificity while maintaining similar sensitivity to Criteria A.ResultsThirty patients (27.3%) were diagnosed with DES after EDCR, while 80 patients (72.7%) were normal. In patients with DES, preoperative TBUT was not different (p = 0.851), but OSDI score was significantly higher (p<0.001). Criteria A showed a sensitivity of 73.3%, specificity of 55.0%, and PPV of 38.0%. Criteria B and C excluded preoperative TBUT, which had no difference between the two groups, and set screening criteria with preoperative OSDI score alone. Criteria B (preoperative OSDI score of 19.6 points or more) showed a sensitivity of 75.0%, specificity of 60.6%, PPV of 41.7% and AUC of 0.739 (p < 0.001). Criteria C was consisted of 5 out of 12 OSDI items that showed significant differences between the two groups; blurred vision, reading, working with a computer, low humidity, and air conditioning. Criteria C (preoperative 5-item OSDI score of 24.4 points or more) was a better predictability, with a sensitivity of 75.0%, specificity of 71.3%, PPV of 49.5%, and AUC of 0.804 (p < 0.001). The AUC of Criteria C was significantly higher than that of Criteria B (p = 0.0037).ConclusionDES occurred after successful EDCR in 27.3% of patients, and an OSDI questionnaire helped to screen DES. The predictability could improve using the modified OSDI score which showed noticeable difference in five OSDI items before and after EDCR.

Dataset Information

A novel serine protease inhibitor as potential treatment for dry eye syndrome and ocular inflammation.

Publications

A novel serine protease inhibitor as potential treatment for dry eye syndrome and ocular inflammation.

Similar Datasets

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