Female patients show better recover y after brain injury and lower incidence of vascular diseases before menopause. The aim of this study was to test the protective effect of female sexual hormones against photostress-induced photoreceptor apoptosis.
Methods
Five week old male albino Sprague-Dawley rats were injected intraperitoneally with progesterone (60 mg/kg body weight) for 4 days. The control group was injected with the vehicle only (benzyl alcohol). Both groups were halved and one was stressed with light (2700 lux for 24 hours) and the other remained under the original dim cyclic light condition. For functional evaluation, baseline electroretinograms (ERGs) were recorded 7 days before light stress, with follow-up ERGs 5 days after the cessation of light exposure. Animals were sacrificed and their eyes enucleated for histology.
Results
Light exposure caused pronounced decrease in the ERG a- and b-wave amplitudes compared to controls. However, in the light-stressed group, the difference in retinal function between progesterone-treated and nontreated animals was not statistically significant. The thickness of the outer nuclear layer and the length of rod outer and inner segments were significantly reduced in the light-stressed group, indicating loss of rod photoreceptor cells. Progesterone had no neuroprotective effect on rod cell structure.
Conclusions
The administration of progesterone did not prove to be protective against excessive light-caused retinal degeneration on male albino rats. The role of other sexual steroids and their interaction need to be clarified.
KannelW.B., ThomT.J.The incidence, prevalence and mortality of cardiovascular disease. In: SchlantR.C., AlexanderR.W., eds. The Heart.New York: McGraw-Hill, 1994; 185–97.
3.
Barrett-ConnorE., BushT.L.Estrogen and coronary heart disease in women. JAMA1991; 265: 1861–7.
4.
GrodsteinF., StampferM.J., MansonJ.E.Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med1996; 335: 453–61.
5.
BäckströmT.Epileptic seizures in women related to plasma estrogen and progesterone during the menstrual cycle. Acta Neurol Scand1976; 54: 321–47.
6.
LandgrenS., BäckströmT., KalistratovG.The effect of progesterone on spontaneous interictal spike evoked by the application of penicillin to the cat's cerebral cortex. J Neurol Sci1978; 36: 119–33.
7.
BäckströmT., ZetterlundB., BlomS., RomanoM.Effects of intravenous progesterone infusions on the epileptic discharge in women with partial epilepsy. Acta Neurol Scand1984; 69: 240–8.
8.
RoofR.L., DuvdevaniR., SteinD.G.Gender influences outcome of brain injury: progesterone plays a protective role. Brain Res1993; 607: 233–6.
9.
RoofR.L., DuvdevaniR., HeyburnJ.W., SteinD.G.Progesterone rapidly decreases brain edema: treatment delayed up to 24 hours is still effective. Exp Neurol1996; 138: 246–51.
10.
WrightD.W., BauerM.E., HoffmanS.W., SteinD.G.Serum progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats. Neurotrauma2001; 18: 901–9.
11.
JiangN., ChoppM., SteinD., FeitH.Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats. Brain Res1996; 735: 101–7.
12.
AlkayedN.J., MurphyS.J., TraystmanR.J., HurnP.D.Neuroprotective effect of female gonadal steroids in reproductively senescent female rats. Stroke2000; 31: 161–8.
WickhamL.A., GaoJ., TodaI., RochaE.M., OnoM., SullivanD.A.Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand2000; 78: 146–53.
18.
LanthierA., PatwardhanV.V.Sex steroids and 5-en-3b-hydroxysteroids in specific regions of the human brain and cranial nerves. J Steroid Biochem1986; 25: 445–9.
19.
LanthierA., PatwardhanV.V.In vitro steroid metabolism by rat retina. Brain Res1988; 463: 403–6.
20.
RobinsonJ., MerryB.J., LightfootM.E., HallA.K.Dynamics of progesterone metabolism in the pseudopregnant rat. J Endocrinol1981; 90: 359–66.
21.
GangradeN.K., BoudinotF.D., PriceJ.C.Pharmacokinetics of progesterone in ovariectomized rats after single dose intravenous administration. Biopharm Drug Dispos1992; 13: 703–9.
22.
NoellW.K., WalkerV.S., KangB.S., BermanS.Retinal damage by light in rats. Invest Ophthalmol1966; 5: 450–73.
23.
ReméC.E., WellerM., SzeczesnyP.Light induced apoptosis in the rat retina in vivo: morphologic features, threshold on a time course. In: AndersonR.E., LaVailM.M., HollyfieldJ.G., eds. Degenerative Diseases of the Retina.New York: Plenum Press; 1995: 19–25.
24.
HafeziH., MartiA., MunzK., ReméC.E.Light-induced apoptosis: differential timing in the retina and pigment epithelium. Exp Eye Res1997; 64: 963–70.
25.
ReméC.E., GrimmC., HafeziF., MartiA., WenzelA.Apoptotic cell death in retinal degenerations. Prog Retinal Eye Res1998; 17: 443–64.
26.
LaVailM.M., GorrinG.M., RepaciM.A.Strain differences in sensitivity to light-induced photoreceptor degeneration in albino mice. Curr Eye Res1987; 6: 825–34.
27.
LanumJ.The damaging effects of light on the retina. Empirical findings, theoretical and practical implications. Surv Ophthalmol1978; 22: 221–49.
28.
LermanS.Photochemical damage. In: eds. Radiant Energy and the Eye.New York: Macmillan Publishing; 1980: 203–11.
29.
LaVailM.M., GorrinG.M., RepaciM.A., YasumuraD.Light-induced retinal degeneration in albino mice and rats: strain and species differences. Prog Clin Biol Res1987; 247: 439–54.
30.
NoellW.K., AlbrechtR.Irreversible effects of visible light on the retina: role of vitamin A. Science1971; 1972: 76–80.
31.
BushR.A., ReméC.E., MalnoeA.Light damage in the rat retina: the effect of dietary deprivation of n-3 fatty acids on acute structural alterations. Exp Eye Res1991; 53: 741–52.
32.
ReméC.E., MalnoeA., JungH.H., WeiQ., MunzK.Effect of dietary fish oil on acute light-induced photoreceptor damage in the rat retina. Invest Ophthalmol Vis Sci1994; 35: 78–90.
33.
KoutzC.A., AndersonR.E., RappL.M., WiegandR.D.Effect of dietary fat and environmental lighting on the response of the rat retina to chronic and acute light stress. Exp Eye Res1995; 60: 307–16.
34.
O'SteenW.K., AndersonK.V., ShearC.R.Photoreceptor degeneration in albino rats: dependency on age. Invest Ophtalmol1974; 13: 334–9.
35.
RappL.M., WilliamsT.P.A parametric study of retinal light damage in albino and in pigmented rats. In: WilliamsT.P., BakerB.N., eds. The Effects of Constant Light on Visual Processes.New York: Plenum Press, 1980; 135–59.
36.
LaVailM.M.Eye pigmentation and constant light damage in the rat retina. In: WilliamsT.P., BakerB.N., eds. The Effects of Constant Light on Visual Processes.New York: Plenum Press, 1980; 357–87.
37.
BarbeM.F., TytellM., GowerD.J., WelchW.J.Hyperthermia protects against light damage in the rat retina. Science1988; 241: 1817–20.
38.
PennJ.S., AndersonR.E.Effect of light history on rod outer-segment membrane composition in the rat. Exp Eye Res1987; 44: 767–78.
39.
PennJ.S., ThumL.A., NaashM.I.Photoreceptor physiology in the rat is governed by the light environment. Exp Eye Res1989; 49: 205–15.
40.
OrganisciakD.T., DarrowR.M., BarsalouL., KuttyR.K., WiggertB.Circadian-dependent retinal light damage in rats. Invest Ophthalmol Vis Sci2000; 41: 3694–701.
41.
O'SteenW.K.Hormonal influences on retinal photodamage. In: WilliamsT.P., BakerB.N., eds. The Effects of Constant Light on Visual Processes.New York: Plenum Press; 1980: 29–49.
42.
O'SteenW.K., DonnellyJ.E.Antagonistic effects of adrenalectomy and ether/surgical stress on light-induced photoreceptor damage. Invest Ophthalmol Vis Sci1982; 22: 1–7.
43.
WiegandR.D., GiustoN.M., RappL.M., AndersonR.E.Evidence for rod outer segment lipid peroxidation following constant illumination of the rat retina. Invest Ophthalmol Vis Sci1983; 24: 1433–5.
44.
GoureauO., JeannyJ.C., BecquetF., HartmannM.P., CourtoisI.Protection against light-induced retinal degeneration by an inhibitor of NO synthase. Neuroreport1993; 5: 233–6.
45.
GrimmC., WenzelA., WilliamsT.P., PascalO.R., HafeziF., ReméC.E.Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching. Invest Ophthalmol Vis Sci2001; 42: 497–508.
46.
LiZ.Y., TsoM.O., WangH.M., OrganisciakD.T.Amelioration of photic injury in rat retina by ascorbic acid: a histopathology study. Invest Ophthalmol Vis Sci1985; 26: 1589–98.
47.
OrganisciakD.T., WangH.M., LiZ.Y., TsoM.O.The protective effect of ascorbate in retinal light damage of rats. Invest Ophthalmol Vis Sci1985; 26: 1580–8.
48.
OrganisciakD.T., DarrowR.M., JiangY-L, MarakG.E., BlanksJ.C.Protection by dimethylthiourea against retinal light damage in rats. Invest Ophthalmol Vis Sci1992; 33: 1599–609.
49.
RanchonI., ChenS., AlvarezK., AndersonR.E.Systemic administration of phenyl-N-tert-butylnitrone protects the retina from light damage. Invest Ophthalmol Vis Sci2001; 42: 1375–9.
50.
RanchonI., WhiteJ., ChenS., AlvarezK., KotakeY., AndersonR.E.Chronic administration of phenyl-N-tert-butylnitrone protects the retina against light damage. In: AndersonR.E., LavailM.M., HollyfieldJ.G., eds. New Insights into Retinal Degenerative Diseases.New York: Plenum Press, 2002; 95–103.
51.
RanchonI., GorrandJ-M, CluzelJ., Droy-LefaixM-T, DolyM.Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract. Invest Ophthalmol Vis Sci1999; 40: 1191–9.
KáldiI., DittmarM., PierceP., AndersonR.E.L-NAME protects against acute light damage in albino rats, but not against retinal degeneration in P23H and S334ter transgenic rats. Exp Eye Res2003; 76: 453–61.
54.
KatzM.L., EldredG.E.Failure of vitamin E to protect the retina against damage resulting from bright cyclic light exposure. Invest Ophthalmol Vis Sci1989; 30: 29–36.
55.
SnodderlyD.M.Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr1995; 62: 1448S–61S.
GaoH., HollyfieldJ.G.Basic fibroblast growth factor: increased gene expression in inherited and light-induced photoreceptor degeneration. Exp Eye Res1996; 62: 181–9.
58.
WenR., SongY., ChengT.Injury-induced upregulation of bFGF and CNTF mRNAs in the rat retina. J Neurosci1995; 15: 7377–85.
59.
CaoW., LiF., SteinbergR.H., LaVailM.M.Development of normal and injury-induced gene expression of aFGF, bFGF, CNTF, BDNF, GFAP and IGF-I in the rat retina. Exp Eye Res2001; 72: 591–604.
60.
FaktorovichE.G., SteinbergR.H., YasumuraD., MatthesM.T., LavailM.M.Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor. Nature1990; 347: 83–6.
61.
FaktorovichE.G., SteinbergR.H., YasumuraD., MatthesM.T., LavailM.M.Basic fibroblast growth factor and local injury protect photoreceptors from light damage in the rat. J Neurosci1992; 12: 3554–67.
62.
LavailM.M., UnokiK., YasumuraD., MatthesM.T., YancopoulosG.D., SteinbergR.H.Multiple growth factors, cytokines and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci USA1992; 89: 11249–53.
63.
LavailM.M., YasumuraD., MatthesM.T.Protection of mouse photoreceptors by survival factors in retinal degenerations. Invest Ophthalmol Vis Sci1998; 39: 592–602.
64.
CaoW., Tombran-TinkJ., EliasR., SezateS., MrazekD., McGinnisJ.F.In vivo protection of photoreceptors from light damage by pigment epithelium-derived factor. Invest Ophthalmol Vis Sci2001; 42: 1646–52.
65.
YuX., RajalaR.V., McGinnisJ.F.Involvement of insulin/phosphoinositide 3-kinase/Akt signal pathway in 17ß-estradiol-mediated neuroprotection. J Biol Chem2004; 279: 13086–94.
