Intraretinal Calcium Channels and Retinal Morbidity in Experimental Retinopathy of Prematurity

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2011 Oct 7

PMID 21976962

Citations 13

Authors

Bruce A Berkowitz

David Bissig

Deborah Bergman

Emanuela Bercea

Vijaya K Kasturi

Robin Roberts

Affiliations

Soon will be listed here.

Abstract

Purpose: To test the hypothesis that intraretinal calcium channels participate in retinal morbidity in a variable oxygen (VO) model of retinopathy of prematurity.

Methods: In control and VO Long Evans (LE) rats, either untreated or treated with voltage- or ligand-gated calcium channel antagonists, we measured retinal neovascular (NV) incidence and severity (adenosine diphosphatase staining), and retinal thickness and intraretinal ion channel activity (manganese-enhanced magnetic resonance imaging). Comparisons with the commonly studied Sprague Dawley rats were performed. Visual performance (optokinetic tracking) in untreated VO LE rats was also evaluated.

Results: In control LE rats, specific L-type voltage calcium channel antagonism, but not ligand-gated channel blockers, suppressed retinal manganese accumulation, while the inhibition of L-type channels normalized intraretinal uptake in VO LE rats. VO LE rats developed more severe NV than VO Sprague Dawley rats. Following VO, both strains demonstrated significant and similar degrees of retinal thinning and supernormal intraretinal manganese uptake. However, over time, intraretinal uptake remained elevated only in VO LE rats. Visual performance was subnormal in VO LE rats. L-type voltage-gated calcium channel antagonism reduced NV severity by 28% (p<0.05) in experimental LE rats compared to that in the control group.

Conclusions: Abnormal intraretinal calcium channel activity is linked with retinal morbidity in experimental retinopathy of prematurity.

Citing Articles

Molecular docking analysis of calcium channel blockers with ALR2 and RAGE.

Kazmi S, Challa S, Alaparthi M, M I, Nagamalla S, Ej P Bioinformation. 2023; 19(1):28-31.

PMID: 37720280 PMC: 10504517. DOI: 10.6026/97320630019028.

Preventing diabetic retinopathy by mitigating subretinal space oxidative stress .

Berkowitz B Vis Neurosci. 2020; 37:E002.

PMID: 32536351 PMC: 7310384. DOI: 10.1017/S0952523820000024.

Applications of Manganese-Enhanced Magnetic Resonance Imaging in Ophthalmology and Visual Neuroscience.

Deng W, Faiq M, Liu C, Adi V, Chan K Front Neural Circuits. 2019; 13:35.

PMID: 31156399 PMC: 6530364. DOI: 10.3389/fncir.2019.00035.

Association of single nucleotide polymorphisms in calcium channel genes with diabetic peripheral neuropathy in Chinese population.

Sun L, Ma J, Mao Q, Yang Y, Ma L, Niu L Biosci Rep. 2018; 38(3).

PMID: 29581247 PMC: 6435562. DOI: 10.1042/BSR20171670.

Systemic Retinaldehyde Treatment Corrects Retinal Oxidative Stress, Rod Dysfunction, and Impaired Visual Performance in Diabetic Mice.

Berkowitz B, Kern T, Bissig D, Patel P, Bhatia A, Kefalov V Invest Ophthalmol Vis Sci. 2015; 56(11):6294-303.

PMID: 26431483 PMC: 4594469. DOI: 10.1167/iovs.15-16990.

References

Prusky G, Harker K, Douglas R, Whishaw I . Variation in visual acuity within pigmented, and between pigmented and albino rat strains. Behav Brain Res. 2002; 136(2):339-48. DOI: 10.1016/s0166-4328(02)00126-2. View

Lutty G, McLeod D . A new technique for visualization of the human retinal vasculature. Arch Ophthalmol. 1992; 110(2):267-76. DOI: 10.1001/archopht.1992.01080140123039. View

Ahlijanian M, Westenbroek R, Catterall W . Subunit structure and localization of dihydropyridine-sensitive calcium channels in mammalian brain, spinal cord, and retina. Neuron. 1990; 4(6):819-32. DOI: 10.1016/0896-6273(90)90135-3. View

Koch K, Kaupp U . Cyclic GMP directly regulates a cation conductance in membranes of bovine rods by a cooperative mechanism. J Biol Chem. 1985; 260(11):6788-800. View

Kirwin S, Kanaly S, Linke N, Edelman J . Strain-dependent increases in retinal inflammatory proteins and photoreceptor FGF-2 expression in streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci. 2009; 50(11):5396-404. DOI: 10.1167/iovs.09-3474. View

OConnor A, Fielder A . Long term ophthalmic sequelae of prematurity. Early Hum Dev. 2008; 84(2):101-6. DOI: 10.1016/j.earlhumdev.2007.11.005. View

Berkowitz B, Gradianu M, Bissig D, Kern T, Roberts R . Retinal ion regulation in a mouse model of diabetic retinopathy: natural history and the effect of Cu/Zn superoxide dismutase overexpression. Invest Ophthalmol Vis Sci. 2008; 50(5):2351-8. PMC: 2688071. DOI: 10.1167/iovs.08-2918. View

Scott S, Kranz J, Cole J, Lincecum J, Thompson K, Kelly N . Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler. 2008; 9(1):4-15. DOI: 10.1080/17482960701856300. View

Dorfman A, Dembinska O, Chemtob S, Lachapelle P . Early manifestations of postnatal hyperoxia on the retinal structure and function of the neonatal rat. Invest Ophthalmol Vis Sci. 2008; 49(1):458-66. DOI: 10.1167/iovs.07-0916. View

10.

Maeng S, Zarate Jr C, Du J, Schloesser R, McCammon J, Chen G . Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2007; 63(4):349-52. DOI: 10.1016/j.biopsych.2007.05.028. View

11.

Berkowitz B, Roberts R, Oleske D, Chang M, Schafer S, Bissig D . Quantitative mapping of ion channel regulation by visual cycle activity in rodent photoreceptors in vivo. Invest Ophthalmol Vis Sci. 2008; 50(4):1880-5. PMC: 2696261. DOI: 10.1167/iovs.08-2958. View

12.

Akula J, Favazza T, Mocko J, Benador I, Asturias A, Kleinman M . The anatomy of the rat eye with oxygen-induced retinopathy. Doc Ophthalmol. 2009; 120(1):41-50. DOI: 10.1007/s10633-009-9198-1. View

13.

Bizzarro M, Hussain N, Jonsson B, Feng R, Ment L, Gruen J . Genetic susceptibility to retinopathy of prematurity. Pediatrics. 2006; 118(5):1858-63. DOI: 10.1542/peds.2006-1088. View

14.

Cheng H, Nair G, Walker T, Kim M, Pardue M, Thule P . Structural and functional MRI reveals multiple retinal layers. Proc Natl Acad Sci U S A. 2006; 103(46):17525-30. PMC: 1859962. DOI: 10.1073/pnas.0605790103. View

15.

Itoh K, Sakata M, Watanabe M, Aikawa Y, Fujii H . The entry of manganese ions into the brain is accelerated by the activation of N-methyl-D-aspartate receptors. Neuroscience. 2008; 154(2):732-40. DOI: 10.1016/j.neuroscience.2008.03.080. View

16.

Bellemann P, Schade A, Towart R . Dihydropyridine receptor in rat brain labeled with [3H]nimodipine. Proc Natl Acad Sci U S A. 1983; 80(8):2356-60. PMC: 393819. DOI: 10.1073/pnas.80.8.2356. View

17.

Prusky G, Silver B, Tschetter W, Alam N, Douglas R . Experience-dependent plasticity from eye opening enables lasting, visual cortex-dependent enhancement of motion vision. J Neurosci. 2008; 28(39):9817-27. PMC: 6671217. DOI: 10.1523/JNEUROSCI.1940-08.2008. View

18.

Bean B . Classes of calcium channels in vertebrate cells. Annu Rev Physiol. 1989; 51:367-84. DOI: 10.1146/annurev.ph.51.030189.002055. View

19.

Pourcho R, Qin P, Goebel D . Cellular and subcellular distribution of NMDA receptor subunit NR2B in the retina. J Comp Neurol. 2001; 433(1):75-85. DOI: 10.1002/cne.1126. View

20.

Schupp D, Merkle H, Ellermann J, Ke Y, Garwood M . Localized detection of glioma glycolysis using edited 1H MRS. Magn Reson Med. 1993; 30(1):18-27. DOI: 10.1002/mrm.1910300105. View