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Effects of melatonin on the nitric oxide treated retina

¹ Division de Neurociencias, Centro de Investigacion Biomedica de Occidente (IMSS), Guadalajara, Jalisco, Mexico
² Laboratory of Experimental Optometry, Department of Optometry and Radiography, The Hong Kong Polytechnic University, Hong Kong, China
³ Department of Cellular and Structural Biology, Mail Code 7762, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA
⁴ Instituto Nacional de Psiquiatria, Departamento de Neurofarmacologia, DIC, Lorenzo Huipulco, Mexico

Correspondence to:
Correspondence to:
A W Siu, PhD
Department of Optometry and Radiography, The Hong Kong Polytechnic University, Kowloon, HKSAR, China; ORSIUA{at}inet.polyu.edu.hk

ABSTRACT
Aims: Nitric oxide (NO) is a free radical which reportedly causes damage to living cells. This study evaluated the damaging effect of NO and the protection of melatonin on the retina in vivo.

Methods: Female Wistar rats (230–250 g) received two intraperitoneal injections of either melatonin (5 mg/kg) or vehicle alone. After general anaesthesia, the animals received 1 µl intravitreal injections of 0.9% saline and 1 mM sodium nitroprusside (SNP) into the right eye and the left eye, respectively. The animals were divided into two groups and then sacrificed after 24 hours (day 1) and 96 hours (day 4). The mean inner retinal layer thickness (mIRLT), the number of retinas expressing hyperchromatic (HC) nuclei in the inner nuclear layer (INL) and the apoptotic ganglion cell detection were compared.

Results: After 1 day, SNP significantly increased the mIRLT by 45% (p = 0.004), initiated more INL nuclear HC expression (p = 0.01) and apoptotic nuclei (p<0.05) compared with the control eyes. Injection of melatonin ameliorated these changes. On day 4, SNP demonstrated similar effects in all parameters on the retina. After the injection of melatonin, both INL HC expression and apoptotic ganglion nuclei in the SNP treated eyes were similar to the controls but the mIRLT was significantly greater than in controls (p = 0.006).

Conclusion: Uncontrolled NO elevation caused morphological and nuclear changes in the retina. Melatonin significantly suppressed the NO induced increase in mIRLT, INL HC expression, and apoptotic ganglion cells on day 1, but not after day 4. Melatonin may have a protective role in the NO elevated retina.

Abbreviations: HC, hyperchromatic; INL, inner nuclear layer; IRLT, inner retinal layer thickness; ONOO^–, peroxynitrite anion; SNP, sodium nitroprusside

Keywords: melatonin; nitric oxide; retina; rabbits