Mechanism of Propofol-Lidocaine Hydrochloride Nano-Emulsion on Retinal Ganglion Cytopathic Effect in Diabetic Rats

The study drew attention to the influence mechanism of propofol and lidocaine hydrochloride nanoemulsion (NE) in the retinal ganglion cell pathology in diabetic rats. Specifically, the propofollidocaine hydrochloride NE was prepared using the emulsification method. The microscope and laser particle size analyser were used to observe the morphology and particle size of NE, respectively. Also, the viscosity of the NE and the recovery rate of the main ingredient were explored. 45 adult male Wistar rats were randomly divided into control group (PBS control), model group (diabetes model), and test group (diabetes model+propofol-lidocaine hydrochloride NE), with 15 rats in each group. The three groups were compared for the blood glucose, body weight, TNF-α and IL-1β mRNA levels in retinal tissue, and the number and apoptosis rate of ganglion cells. It was found that the average particle size of the NE was 89.76 nm, the maximum absorption wavelength was 280.0 nm, and the viscosity was 106.49 N/m/s. The average recovery rate of propofol in NE was 99.91%, and that of lidocaine hydrochloride was 99.80%. At 12th week after modeling, the blood glucose of the test group was lower versus the model group (P < 0.05); the blood glucose and body weight of rats in the control group were lower than those in the other two groups (P < 0.001). The test group exhibited lower mRNA levels of TNF-α and IL-1β and apoptosis index of retinal ganglion cells versus the model group (P < 0.05). The model group showed a lower number of retinal ganglion cells versus the other two groups (P < 0.05). It was inferred that propofol-lidocaine hydrochloride NE of a small particle size and good syringeability can notably reduce blood glucose, TNF-α and IL-1β mRNA levels, and retinal ganglion cell apoptosis index, and at the same time increase the number of retinal ganglion cells.

The change of microglia numbers within the mice retina, optic nerve and chiasm following intravitreal AAV2-GFP injection

Purpose To explore the optimized concentration of AAV2-GFP for sparse transfection of retinal ganglion cells (RGCs) and optic nerve (ON), and to examine the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after injection. Methods We defined the optimal concentration of AAV2-GFP for sparse labeling of RGCs and axons in WT mice. We further explored the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after intravitreal injection in CX3CR1+/GFP mice. Results 14 days after intravitreal injection of AAV2-GFP, live imaging of the retina showed that fundus fluorescence was very strong and dense at 2.16 × 1011 VG/retina, 2.16 × 1010 VG/retina, 2.16 × 109 VG/retina. RGCs were sparsely marked at a concentration 1:1000 (2.16 × 108 VG/retina) and fundus fluorescence was weak. The transfected RGCs and axons were unevenly distributed in the retina and significantly more RGCs were transfected near the injection site of AAV2-GFP compared to the other sites of the flat-mounted retina. Microglia density increased significantly in the retina and part of optic nerve, but not in the optic chiasm. The morphology of microglia was largely unchanged. Conclusions AAV2-GFP was highly efficient and the optimal concentration of sparsely labeled RGCs was 1:1000 (2.16 × 108 VG/retina). After intravitreal injection of AAV2-GFP, the number of microglia increased partly. The morphology of microglia was comparable.

Peroxisome Proliferator-Activated Receptor α Activation Protects Retinal Ganglion Cells in Ischemia-Reperfusion Retinas

Background and Objective: Retinal ischemia-reperfusion (IR) leads to massive loss of retinal ganglion cells (RGC) and characterizes several blind-causing ophthalmic diseases. However, the mechanism related to retinal IR is controversial, and a drug that could prevent the RGC loss caused by IR is still lacking. This study aimed to investigate the role of endogenous retinal peroxisome proliferator-activated receptor (PPAR)α and the therapeutic effect of its agonist, fenofibric acid (FA), in IR-related retinopathy.Materials and Methods: Fenofibric acid treatment was applied to the Sprague–Dawley rats with IR and retinal cell line 28 cells with oxygen-glucose deprivation (OGD) (an in vitro model of IR). Western blotting, real-time PCR, and immunofluorescence were used to examine the expression levels of PPARα, glial fibrillary acidic protein (GFAP), and cyclooxygenase-2 (COX2). Hematoxylin and eosin (HE) staining, propidium iodide (PI) staining, retrograde tracing, and flash visual-evoked potential (FVEP) were applied to assess RGC injury and visual function.Results: Retinal IR down-regulated PPARα expression in vitro and in vivo. Peroxisome proliferator-activated receptor α activation by FA promoted survival of RGCs, mitigated thinning of the ganglion cell complex, and decreased the latency of positive waves of FVEPs after IR injury. Further, FA treatment enhanced the expression of endogenous PPARα and suppressed the expression of GFAP and COX2 significantly.Conclusion: Peroxisome proliferator-activated receptor α activation by FA is protective against RGC loss in retinal IR condition, which may occur by restoring PPARα expression, inhibiting activation of glial cells, and suppressing retinal inflammation. All these findings indicate the translational potential of FA in treating IR-related retinopathy.