Neuroprotective Effect of Intravitreal Single-Dose Lithium Chloride after Optic Nerve Injury in Rats

ABSTRACT

Objective

Lithium is an old drug to control bipolar disorder. Moreover, it presents neuroprotective effects and supports neuronal plasticity. The aim of this study was to evaluate neuroprotective effect of intravitreal lithium after optic nerve injury.

Methods

Three dosages of lithium chloride, including 2 pmol, 200 pmol, and 2 nmol, were injected intravitreally after rat optic nerve injury. Proteins expression were assessed by western blot. Nitric oxide (NO) metabolites were measured by Griess test. Visual evoked potential (VEP) and optical coherence tomography (OCT) measurement were performed after trauma induction, in addition to H & E and TUJ1 staining of ganglion cells.

Results

Western blot depicted lithium can significantly increase antiapoptotic Bcl-2 protein level and reduce p-ERK, Toll-like receptor 4 (TLR4) and proapoptotic proteins such as Bax level in retinal tissue and Griess test reflected that NO metabolites level decreased in lithium treated eyes (P < .05). While, OCT showed no significant changes (P = .36 and P = .43 comparing treated group with trauma) in retinal ganglion cell layer thickness after lithium injection, VEP P2 wave amplitude increased significantly (P < .01) in lithium-treated eyes and its latency reduced (P < .05 for N1 wave and P < .01 for P2 wave). Tuj1 antibody-labeled retinal ganglion cells analyzing showed that the number of retinal ganglion cells were significantly higher in lithium treated eyes compared to untreated eyes with optic nerve injury.

Conclusion

It seems intravitreally lithium has optic nerve neuroprotective effects by various mechanisms like overexpression of antiapoptotic proteins, suppressing proinflammatory molecules and proapoptotic factors, and decreasing nitric oxide.

KEYWORDS:

• Lithium chloride
• rat optic nerve injury
• ganglion cell
• Bcl2/Bax

Contribution

In this study every member respectively performed these responsibilities:

Moein Ala (surgery and following animals, writing the article), Razieh Mohammad Jafari (Western blot performance and editing assay and consulted methods), Hossein Nematian (surgery), Masoud Aghsaei Fard (OCT measurement and consultation of study, editing assay, corresponding author), Mohammad Reza Ganjedanesh (surgery), Asieh Naderi (VEP measurement, editing assay), Mostafa Akbariani (providing antibodies and facilitating western blot), Mehdi Sanatkar (coordinate and review the manuscript), Leila Satarian (Tuj1 assay), and Ahmad Reza Dehpour (supervised and principal investigator).

Conflicts of interest

Authors indicate that there is no conflict of interest.

Additional information

Funding

This work was supported by a grant from Experimental Medicine Research Center, Tehran University of Medical Sciences [Grant No. 94-01-30-28247] and Iran National Science Foundation (INSF) [Grant No. 96002757].