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.