Cornea - ARVO

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Corneaphenotype data provided by LSCM, we didn’t demonstrate the impactof population difference on MG morphological pattern, noassociation was found between genotype and phenotype.Due to small sample size and other reasons, we didn't get outcomesconsistent with those in previous animal experiments. Furtherpopulation-based association studies need to be carried out tounequivocally test our hypothesis and reach a definite conclusion.FIGURE 1. Meibomian glandular acinar units imaged by LSCM.(A)Chinese; (B)Uyghur;(C)European.TABLE 1. Correlation between EDAR V370A and MGsCommercial Relationships: Yujing YANG, None; JianJiang Xu,None; Jiaxu Hong, NoneProgram Number: 924 Poster Board Number: B0229Presentation Time: 1:00 PM - 2:45 PMNotch regulation of PPAR-gamma and development ofmeibomian gland dysfunctionMindy K. Call, Katy Fischesser, Matthew O. Lunn, Winston Kao.Ophthalmology, University of Cincinnati, Cincinnati, OH.Purpose: Meibomian gland dysfunction (MGD) is a chronic, diffuseabnormality of the meibomian glands, which is characterized byterminal duct obstruction and/or qualitative/quantitative changes inglandular secretion resulting in alterations of the tear film, eyeirritation and inflammation. One particular molecule thought to playan important role in lipid secretion is peroxisome proliferatoractivated receptor gamma (PPARλ). Given the importance of PPARλin lipid metabolism, this study aims to elucidate its role in meibomiangland formation/function and the development of MGD. Thehypothesis is that loss of PPARλ will disrupt meibomian glandformation/function resulting in a hyposecretory state. In addition thisstudy will examine the role of Notch signaling in regulating PPARλexpression.Methods: Transgenic animals, utilizing both Le-cre and K14-rtTAdriver mice, were used to ablate PPARλ and Jag1 and to expressdnMAML. Animals were examined for signs of MGD/dry eye viatear solution assessment, HRT II, slit lamp, lissamine green staining,oil red O staining and lyve 1 staining. In addition, eyes were collectedat various time points to assess expression of Notch signalingcomponents. All reported research was conducted in compliance withthe ARVO Statement for the Use of Animals in Ophthalmic andVision Research and approved by the IACUC of the University ofCincinnati.Results: Loss of PPARλ resulted in abnormalities in meibomiangland morphogenesis leading to dry eye-like symptoms. Specificallythere was an increase in the number of cell layers lining each acinus,fewer and more condensed lipid droplets, “swollen” eyelids,increased protein concentration in the tears and increasedlymphangiogenesis. Inhibition of the notch signaling pathway usingdnMAML mice resulted in a significant meibomian gland defect.With a phenotype similar to what was seen in the absence of PPARλ.Loss of Jag1 did not have as profound of an effect on meibomiangland formation or function, which may be explained bycompensation by other Notch ligands.Conclusions: Together these data, suggest that PPARλ is critical forthe proper formation and function of the meibomian glands and alsodemonstrate a mouse model that can be used to study MGD. Notchsignaling also appears to be an important regulator of PPARλ.Commercial Relationships: Mindy K. Call, None; KatyFischesser, None; Matthew O. Lunn, None; Winston Kao, NoneSupport: from NIH/NEI EY013755, Research to Prevent Blindness,Ohio Lions Eye Research FoundationProgram Number: 925 Poster Board Number: B0230Presentation Time: 1:00 PM - 2:45 PMTear Meniscus Dimensions and Location of Marx’s Line inMeibomian Gland DysfunctionJason Feuerman, Stephen C. Pflugfelder. Ophthalmology, BaylorCollege of Medicine, Houston, TX.Purpose: In patients with tear film instability and meibomian glanddysfunction (MGD), Marx’s line (ML) is often displaced anteriorly.Bron, et al, suggest that ML may be formed as a result of a relativelyincreased solute concentration at the peripheral apex of the tearmeniscus, which may thus play a significant role in thepathophysiology of primary MGD. We hypothesized that tearmeniscus height, area, and length of anterior excursion along the lidmargin positively correlate with the extent of anterior migration ofML in patients with MGD.Methods: We performed a retrospective analysis of consecutivepatients with eye irritation symptoms, MGD with tear film instability,no aqueous tear deficiency, and eyelid photographs and OCTs ofsufficient quality for analysis. 32 eyes of 17 patients were included.Photographs of lissamine green-stained lower eyelids were analyzedusing the ImageJ analysis software. The furthest anterior migration ofML was measured in 3 zones: temporal, central, and nasal. For eacheye, the tear meniscus height, area, and length of anterior excursion atthe center of the lower eyelid were measured using Fourier-DomainRTVue-100 optical coherence tomography (OCT). Spearmancorrelation analysis was performed.Results: The mean eye age was 68 ± 10 years. In the temporal zone,there was a statistically significant positive correlation between thefurthest anterior migration of ML and the central tear meniscus height(r = 0.468, p = 0.007), area (r = 0.492, p = 0.004), and anteriorexcursion (r = 0.448, 0.010). In the central zone and the nasal zonethere was no significant correlation between the furthest anteriormigration of ML and any of the OCT measurements.Conclusions: In patients with symptomatic MGD, central tearmeniscus height, area, and anterior excursion positively correlatewith the furthest anterior migration of ML in the temporal zone, butnot in the central or nasal zone. A possible explanation is that agingchanges such as conjunctivochalasis, which tends to be morepronounced temporally, physically impedes lateral tear migrationleading to increased central tear pooling, while also promotinganterior excursion of the tear meniscus temporally by acting as abridge. By this process, the solute gradient mechanism couldcontribute to the initiation of MGD. MGD could also just be initiatedby increased exposure of meibomian gland orifices to tears,regardless of their osmolarity.Commercial Relationships: Jason Feuerman, None; Stephen C.Pflugfelder, Allergan (C), Glaxo Smith Kline (C), Bausch and Lomb(C), Baylor College of Medicine (P)©2013, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permissionto reproduce any abstract, contact the ARVO Office at arvo@arvo.org.