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This abstract is assigned to session OB Free papers 5 - Miscellaneous

Title

FRO - The effect of upregulated LOX and LOXL2 on inflammation and fibrosis in a laser induced CNV model

Purpose	Lysyl oxidase (LOX) and lysyl oxidase-like protein 2 (LOXL2) are involved in the cross-linking of collagen and elastin in the extracellular space. Therefore, these proteins play a major role in the process of fibrosis. This study was designed to elucidate the role of LOX and LOXL2 in inflammation and fibrosis after choroidal neovascularization (CNV).
Methods	CNV was induced in 8 to 10 weeks old C75Bl/6 mice (n = 5 per timepoint), by placing 3 laser spots at 9, 12 and 3 o’clock position (50µm, 0.05 s and 400mW). Mice were sacrificed 2, 4, 7, 14, 28 and 35 days after lasering. LOX and LOXL2 expression in choroid and retina was analyzed by using quantitative real time RT-PCR. Inflammation was studied by an immunohistochemical staining for CD45; fibrosis was evaluated by a Sirius Red and Trichrome staining.
Results	Both LOX and LOXL2 were significantly increased over time in the choroid and retina of lasered mice. LOX was 2.1, 3.2, 1.75, 1.3, 2 and 1.3 times upregulated on day 2, 4, 7, 14, 28 and 35 after laser, respectively, compared to the expression of LOX in non-lasered eyes. LOXL2 was 1.1, 1.6, 1.3, 1.1, 1.5 and 1.2 times upregulated on day 2, 4, 7, 14, 28 and 35 after laser, respectively, versus LOXL2 expression in non-lasered eyes. On day 2 and 4 after laser, the number of inflammatory cells was increased by 16% compared to control. Both Sirius Red and Thrichrome staining showed a significant increase of collagen deposition in the choroid on day 14 (43%), day 28 (44%) and day 35 (40%) after laser compared to non-lasered eyes.
Conclusion	A biphasic upregulation of LOX and LOXL2 was observed after CNV induction, which was associated with the inflammatory and fibrotic phase, respectively. Our data suggests that LOX and LOXL2 play a role in the process of inflammation and fibrosis after the induction of CNV. Our proposed research will elucidate the efficacy of anti-LOX and/or anti-LOXL therapy in CNV and will highlight any anti-angiogenic, anti-inflammatory, and/or anti-fibrotic effects.

Author 1

Last name	VAN DE VEIRE
Initials	S
City	Leuven