Effect of para-aminobenzoic acid on morphologic changes of the retina in the rd10 mouse model of retinitis pigmentosa

Purpose: Histological evaluation of the influence of PABA on the course of retinal degeneration and the state of outer nuclear layer (ONL) of the retina in rd10 mice.
Methods: the present experiment studied PR model in rd10 mice (Jackson Labs, Maine, USA) homozygous for a recessive mutation in the b-subunit of rod phosphodiesterase. Animals in the treatment group (n = 28) were intraperitoneally injected with PABA in saline (50 mg/kg) 6 times a week from the third day after birth till 4.5 weeks of age. Animals in the control group (n = 24) were intraperitoneally injected with saline using the same protocol. At 3 and 4.5 weeks of age, eyes were enucleated. After fixation and dehydration, the samples were placed in paraffin and serial sections, 4 microns sick, were obtained through the center of the optic nerve. thickness of ONL and the number of rows of photoreceptor nuclei in the ONL of central, middle and peripheral parts of the retina were analyzed to access the morphological condition of retina. t-test was used to compare the dif- ference between two groups (p ≤ 0.05, unpaired two-tailed t-test).
Results: At the age of three weeks, the thickness of ONL and the number of rows of photoreceptor nuclei in the ONL is reducing more than twofold in both experimental groups compared with healthy mice group. there is a tendency toward greater thickness of the ONL and the greater number of rows of nuclei in the central zone and mid-peripheral retina at the age of three weeks in the group of animals that were injected with PABA compared to the control group. At the age of 4.5 weeks both the thickness of the ONL, and the number of rows of photoreceptor nuclei in the ONL were significantly greater in the peripheral retina of the animals in the treatment group compared with the control group (p <0.05).
Conclusion: Systemic administration of PABA has a stabilizing effect on the degenaration process of ONL of the retina in rd10 mice. thus, PABA, with its good safety profile can be an effective addition to the antioxidant therapy of retinitis pigmentosa. 

1. Dalke C, Löster J, Fuchs H. et al. Electroretinography as a screening method for muta- tions causing retinal dysfunction in mice // Invest Ophthalmol Vis Sci. — 2004. –Vol. 45. — P. 601-609.

2. Wang DY, Chan WM, Tam PO, et al. Gene mutations in retinitis pigmentosa and their clinical implications.Clin Chim Acta // 2005.— Vol. 351.— P. 5-16.

3. MarigoV. Programmed cell death in retinal degeneration: targeting apoptosis in photo- receptors as potential therapy for retinal degeneration // Cell Cycle. — 2007. — Vol. 6. — P. 652-5. Epub 2007 Mar 17.

4. Chang B, Hawes NL, Hurd RE, et al. Retinal degeneration mutants in the mouse // Vi- sion Res. — 2002. — Vol. 42. — P. 517-525.

5. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa // Lancet. — 2006. — Vol. 368. — P. 1795-1809.

6. Padnick-Silver, L., Derwent, J. J., Giuliano, E., et al. Retinal oxygenation and oxygen me- tabolism in Abyssinian cats with a hereditary retinal degeneration // Invest. Ophthal- mol. Vis. Sci. — 2006. — Vol. 47. — P. 3683-3689.

7. Ahuja-Jensen, P., Johnsen-Soriano, S., Ahuja, S., et al. Low glutathione peroxidase in rd1 mouse retina increases oxidative stress and proteases // Neuroreport. — 2007. — Vol. 18. — P. 797-801.

8. Komeima, K., Rogers, B. S., Campochiaro, P. A. Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa // J. Cell. Physiol. — 2007. — Vol. 213. — P. 809-815.

9. Акберова С. И., Ершов Ф. И., Мусаев Галбинур П. И. и др. Динамика интерфероново- го статуса у больных с герпетическими кератитами при лечении нового индукто-

10. ра интерферона актиполом // Вестн. офтальмологии. — 2001. — No 1. — С. 33-36.

11. Дрозд Н. Н., Акберова С. И., Строева О. Г. и др. Антитромботическая активность пара-аминобензойной кислоты // Эксп. клин. фармакол. — 2000. — No 3. — С. 40-44.

12. Акберова С. И., Строева О. Г., Магомедов Н. М. и др. Cравнительная оценка антиок- сидантной активности парааминобензойной кислоты и эмоксипина в роговице и хрусталике (экспериментальные исследования) // Вестн. офтальмол. — 2001. — No 4. — С. 25-29.

13. Акберова С. И., Строева О. Г., Магомедов Н. М. и др. Cравнительная оценка антиоксидантной активности парааминобензойной кислоты и эмоксипина в сетчатке // Вестн. офтальмол. — 1998. — No 6. — С. 39-44.

14. Строева О. Г., Поплинская В. А., Хорошилова-Маслова И. П. и др. Стимуляция образования мембранных дисков наружных сегментов фоторецепторных клеток сет- чатки у крыс с помощью парааминобензойной кислоты // ДАН-СССР. — 1990. — Т. 314. — No 2. — С. 483-487.

15. Gargini, C., Terzibasi, E., Mazzoni, F., et al. Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study // J. Comp. Neurol. — 2007. — Vol. 500. — P. 222-238.

16. Komeima, K., Rogers, B. S., Lu, L., et al. Antioxidants reduce cone cell death in a model of retinitis pigmentosa // Proc. Natl Acad. Sci. USA. — 2006. — Vol. 103. — P. 11300-11305.

17. Sanz, M. M., Johnson, L. E., Ahuja, S., et al. Significant photoreceptor rescue by treatment with a combination of antioxidants in an animal model for retinal degeneration // Neu- roscience. — 2007. — Vol. 145. — P. 1120-1129.