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Vascular Adhesion Protein-1 Blockade Suppresses Ocular Inflammation After Retinal Laser Photocoagulation in Mice
Takashi Matsuda1, Kousuke Noda2, Miyuki Murata2
1Laboratory of Ocular Cell Biology & Visual Science, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Purpose:
To investigate the effect of the vascular adhesion protein-1 (VAP-1) inhibitor RTU-1096 on retinal morphologic changes and ocular inflammation after retinal laser photocoagulation in mice.
Methods:
C57BL/6JJcl mice were fed a diet containing RTU-1096, a specific inhibitor for VAP-1, or a control diet ad libitum for 7 days. Laser photocoagulation was performed on the peripheral retina of the animals. The semicarbazide sensitive amine oxidase (SSAO) activities in plasma and chorioretinal tissues were measured. Optical coherence tomography (OCT) images were acquired before and at 1, 3, and 7 days after laser photocoagulation, and thickness of the individual retinal layers was measured. Intravitreal leukocyte infiltration was assessed by histologic analysis. The expression level of intercellular adhesion molecule-1 (ICAM-1) in retinal tissues were examined by quantitative real-time PCR.
Results:
One day after laser photocoagulation, the thickness of the outer nuclear layer (ONL) increased in the laser group compared with in the control group, and RTU-1096 administration abrogated the ONL thickening. Histologic analysis and OCT observation revealed that laser photocoagulation caused infiltration of inflammatory cells and the appearance of hyperreflective foci at the vitreoretinal surface, both of which were suppressed by RTU-1096 administration. In addition, systemic administration of RTU-1096 reduced upregulation of the leukocyte adhesion molecules ICAM-1 in the retina.
Conclusions:
The current data indicate that VAP-1/SSAO inhibition may be a potential therapeutic strategy for the prevention of macular edema secondary to scatter laser photocoagulation in patients with ischemic retinal diseases such as diabetic retinopathy.
Insights
Vascular adhesion protein-1 (VAP-1) inhibition with RTU-1096 reduced retinal swelling and inflammation after laser injury in mice. This suggests VAP-1/SSAO inhibition is a promising strategy for treating laser-induced macular edema.
Area of Science:
- Ophthalmology
- Retinal Diseases
- Pharmacology
Background:
- Vascular adhesion protein-1 (VAP-1) plays a role in inflammation.
- Laser photocoagulation can induce retinal changes and inflammation.
Purpose of the Study:
- To evaluate the efficacy of RTU-1096, a VAP-1 inhibitor, in mitigating retinal morphologic changes and inflammation post-laser photocoagulation in a mouse model.
Main Methods:
- Mice received RTU-1096 or a control diet before laser photocoagulation.
- Retinal thickness was measured using optical coherence tomography (OCT).
- Inflammation and gene expression of adhesion molecules were assessed histologically and via qPCR.
Main Results:
- RTU-1096 treatment prevented outer nuclear layer thickening after laser injury.
- RTU-1096 suppressed inflammatory cell infiltration and vitreoretinal hyperreflective foci.
- RTU-1096 reduced the upregulation of intercellular adhesion molecule-1 (ICAM-1) in retinal tissues.
Conclusions:
- VAP-1/SSAO inhibition with RTU-1096 demonstrates therapeutic potential.
- This approach may prevent macular edema following scatter laser photocoagulation in ischemic retinal diseases like diabetic retinopathy.
