title: Neuroprotective effect of minocycline in a rat model of branch retinal vein occlusion.
abstract: Branch retinal vein occlusion (BRVO) is the second most frequent retinal vascular disorder. Currently the first-line therapies for BRVO include anti-VEGF and dexamethasone implant treatment, however, with direct or indirect damage on retinal neurons, it has limited effect in improving patients visual acuity. Therefore, novel treatments with neuroprotective effect for BRVO retina were expected. Minocycline is a semisynthetic, broad spectrum tetracycline antibiotic with high penetration through the blood brain barrier. The neuroprotective effects of minocycline have been shown in various central nervous system (CNS) disease. Since both CNS and retina were composed of neurons and glials, it is reasonable to expect a neuroprotective effect by minocycline for BRVO retina. Therefore, the aim of the present study was to study whether minocycline has neuroprotective effect in branch retinal vein occlusion (BRVO) and the possible underlying molecular basis. We created BRVO in rats using laser photocoagulation. The animals were then randomly divided into 4 groups to evaluate the effect of minocycline: group A: minocycline 45 mg/kg intraperitoneal injection (i.p.), group B: minocycline 90 mg/kg i.p., group C: normal saline i.p., group D: sham injection. Fundus photography and fluorescein angiography (FA) were conducted. The changes in thickness of retinal layers were measured with optical coherence tomography (OCT) in vivo. We found that retinal edema occurred predominantly in the inner retinal layers. Intraperitoneal administration of minocycline significantly ameliorated retinal edema in the early stage of BRVO. We performed Full field Electroretinography (ffERG) to evaluate retinal function and found that the reduction of b wave amplitude decreased in the combined maximal response. The expressional levels of apoptosis related genes (Bax, Bcl-2) and inflammation related genes (IL-1 β, TNF α, MCP-1 and CCR2) were measured by real-time PCR, the results showed that minocycline treatment upregulated Bcl-2 expression and inhibits TNF α expression since early stage of BRVO. We also performed Hematoxylin-Eosin (HE) and immunostaining for Iba 1 (a microgilal marker), active caspase-3, Bax, Bcl-2, IL-1 β, TNF α and found that minocycline inhibits retinal microglial activation, prevents retinal ganglion cell loss, and inhibits retinal caspase-3 activation. Thus, our study indicates that systemic administration of minocycline ameliorates retinal edema and preserves retinal function in the early stage of BRVO possibly via inhibiting microglia activation and protecting RGC from apoptosis.
authors.affiliation: Department of Ophthalmology, People's Hospital, Peking University, Beijing, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Sun
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Li
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: He
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007274:Injections, Intraperitoneal; D017628:Microglia / Q000187:drug effects*; D008911:Minocycline / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010211:Papilledema / Q000503:physiopathology / Q000517:prevention & control*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D011914:Rats, Inbred BN; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012170:Retinal Vein Occlusion / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; C494828:Bax protein, rat; D016207:Cytokines; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008911:Minocycline
keywords: branch retinal vein occlusion; minocycline; neuroprotective; rat