Abstract
The retina is one of the tissues with the highest metabolic activity in the body, and the energy-demanding photoreceptors require appropriate oxygen levels for photo- and neurotransduction. Accumulating evidence suggests that age-related changes in the retina may reduce oxygen supply to the photoreceptors and trigger a chronic hypoxic response. A detailed understanding of the molecular response to hypoxia is crucial, as hindered oxygen delivery may contribute to the development and progression of retinal pathologies such as age-related macular degeneration (AMD). Important factors in the cellular response to hypoxia are microRNAs (miRNAs), which are small, noncoding RNAs that posttranscriptionally regulate gene expression by binding to mRNA transcripts. Here, we discuss the potential role of hypoxia-regulated miRNAs in connection to retinal pathologies.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AMD :
-
Age-related macular degeneration
- Cyr61 :
-
Cysteine-rich protein 61
- Efna3 :
-
Receptor-tyrosine kinase ligand ephrin-A3
- HIFs :
-
Hypoxia-inducible transcription factors
- HypoxamiRs :
-
Hypoxia-regulated miRNAs
- ISCU :
-
Iron-sulfur cluster assembly enzyme
- miRNAs :
-
MicroRNAs
- OIR :
-
Oxygen-induced retinopathy
- Ptp1b :
-
Protein tyrosine phosphatase, non-receptor type 1
- RISC :
-
RNA-induced silencing complex
- ROP :
-
Retinopathy of prematurity
- Vegf :
-
Vascular endothelial growth factor
References
Agrawal S, Chaqour B (2014) MicroRNA signature and function in retinal neovascularization. World J Biol Chem 5:1–11
Arjamaa O, Nikinmaa M, Salminen A et al (2009) Regulatory role of HIF-1 a in the pathogenesis of age-related macular. Ageing Res Rev 8:349–358
Barben M, Schori C, Samardzija M et al (2018a) Targeting Hif1a rescues cone degeneration and prevents subretinal neovascularization in a model of chronic hypoxia. Mol Neurodegener 13:12
Barben M, Ail D, Storti F et al (2018b) Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress. Cell Death Differ 25:2071
Bartel DP (2018) Metazoan microRNAs. Cell 173:20–51
Berber P, Grassmann F, Kiel C et al (2017) An eye on age-related macular degeneration: the role of microRNAs in disease pathology. Mol Diagn Ther 21:31–43
Bhattacharjee S, Zhao Y, Dua P et al (2016) microRNA-34a-mediated down-regulation of the microglial-enriched triggering receptor and phagocytosis-sensor TREM2 in age-related macular degeneration. PLoS One 11:e0150211
Boldin MP, Baltimore D (2012) MicroRNAs, new effectors and regulators of NF-kappaB. Immunol Rev 246:205–220
Bruning U, Cerone L, Neufeld Z et al (2011) MicroRNA-155 promotes resolution of hypoxia-inducible factor 1alpha activity during prolonged hypoxia. Mol Cell Biol 31:4087–4096
Camps C, Buffa FM, Colella S et al (2008) hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin Cancer Res 14:1340–1348
Chan YC, Khanna S, Roy S et al (2011) miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J Biol Chem 286:2047–2056
Chan YC, Banerjee J, Choi SY et al (2012) miR-210: the master hypoxamir. Microcirculation 19:215–223
Chan-Ling T, Gock B, Stone J (1995) The effect of oxygen on vasoformative cell division. Evidence that ‘physiological hypoxia’ is the stimulus for normal retinal vasculogenesis. Invest Ophthalmol Vis Sci 36:1201–1214
Chen Z, Li Y, Zhang H et al (2010) Hypoxia-regulated microRNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 29:4362–4368
Chung SH, Gillies M, Yam M et al (2016) Differential expression of microRNAs in retinal vasculopathy caused by selective Muller cell disruption. Sci Rep 6:28993
Dallinger S, Findl O, Strenn K et al (1998) Age dependence of choroidal blood flow. J Am Geriatr Soc 46:484–487
Devlin C, Greco S, Martelli F et al (2011) miR-210: more than a silent player in hypoxia. IUBMB Life 63:94–100
Ertekin S, Yildirim O, Dinc E et al (2014) Evaluation of circulating miRNAs in wet age-related macular degeneration. Mol Vis 20:1057–1066
Fasanaro P, D'Alessandra Y, Di Stefano V et al (2008) MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 283:15878–15883
Grassmann F, Schoenberger PG, Brandl C et al (2014) A circulating microRNA profile is associated with late-stage neovascular age-related macular degeneration. PLoS One 9:e107461
Grimm C, Hermann DM, Bogdanova A et al (2005) Neuroprotection by hypoxic preconditioning: HIF-1 and erythropoietin protect from retinal degeneration. Semin Cell Dev Biol 16:531–538
Hackler L Jr, Wan J, Swaroop A et al (2010) MicroRNA profile of the developing mouse retina. Invest Ophthalmol Vis Sci 51:1823–1831
Hu S, Huang M, Li Z et al (2010) MicroRNA-210 as a novel therapy for treatment of ischemic heart disease. Circulation 122:S124–S131
Ivan M, Huang X (2014) miR-210: fine-tuning the hypoxic response. Adv Exp Med Biol 772:205–227
Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–D73
Krol J, Krol I, Alvarez CP et al (2015) A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture. Nat Commun 6:7305
Kurihara T, Westenskow PD, Gantner ML et al (2016) Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration. elife 5:e14319
Lam AK, Chan ST, Chan H et al (2003) The effect of age on ocular blood supply determined by pulsatile ocular blood flow and color Doppler ultrasonography. Optom Vis Sci 80:305–311
Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854
Ling S, Birnbaum Y, Nanhwan MK et al (2013) MicroRNA-dependent cross-talk between VEGF and HIF1alpha in the diabetic retina. Cell Signal 25:2840–2847
Liu CH, Wang Z, Sun Y et al (2016) Retinal expression of small non-coding RNAs in a murine model of proliferative retinopathy. Sci Rep 6:33947
Loscher CJ, Hokamp K, Kenna PF et al (2007) Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa. Genome Biol 8:R248
Loscher CJ, Hokamp K, Wilson JH et al (2008) A common microRNA signature in mouse models of retinal degeneration. Exp Eye Res 87:529–534
McArthur K, Feng B, Wu Y et al (2011) MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes 60:1314–1323
McCormick RI, Blick C, Ragoussis J et al (2013) miR-210 is a target of hypoxia-inducible factors 1 and 2 in renal cancer, regulates ISCU and correlates with good prognosis. Br J Cancer 108:1133–1142
Murray AR, Chen Q, Takahashi Y et al (2013) MicroRNA-200b downregulates oxidation resistance 1 (Oxr1) expression in the retina of type 1 diabetes model. Invest Ophthalmol Vis Sci 54:1689–1697
Nallamshetty S, Chan SY, Loscalzo J (2013) Hypoxia: a master regulator of microRNA biogenesis and activity. Free Radic Biol Med 64:20–30
Nguyen TA, Jo MH, Choi YG et al (2015) Functional anatomy of the human microprocessor. Cell 161:1374–1387
Nunes DN, Dias-Neto E, Cardo-Vila M et al (2015) Synchronous down-modulation of miR-17 family members is an early causative event in the retinal angiogenic switch. Proc Natl Acad Sci U S A 112:3770–3775
Semenza GL (2004) Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda) 19:176–182
Shen J, Yang X, Xie B et al (2008) MicroRNAs regulate ocular neovascularization. Mol Ther 16:1208–1216
Shen G, Li X, Jia YF et al (2013) Hypoxia-regulated microRNAs in human cancer. Acta Pharmacol Sin 34:336–341
Tan JR, Koo YX, Kaur P et al (2011) microRNAs in stroke pathogenesis. Curr Mol Med 11:76–92
Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75:855–862
Winter J, Jung S, Keller S et al (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234
Wu JH, Gao Y, Ren AJ et al (2012) Altered microRNA expression profiles in retinas with diabetic retinopathy. Ophthalmic Res 47:195–201
Yan L, Lee S, Lazzaro DR et al (2015) Single and compound knock-outs of microRNA (miRNA)-155 and its angiogenic gene target CCN1 in mice alter vascular and neovascular growth in the retina via resident microglia. J Biol Chem 290:23264–23281
Zhang Y, Fei M, Xue G et al (2012) Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease. J Cell Mol Med 16:249–259
Zhuang Z, Xiao q HH et al (2015) Down-regulation of microRNA-155 attenuates retinal neovascularization via the PI3K/Akt pathway. Mol Vis 21:1173–1184
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this paper
Cite this paper
Barben, M., Bordonhos, A., Samardzija, M., Grimm, C. (2019). Hypoxia-Regulated MicroRNAs in the Retina. In: Bowes Rickman, C., Grimm, C., Anderson, R., Ash, J., LaVail, M., Hollyfield, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1185. Springer, Cham. https://doi.org/10.1007/978-3-030-27378-1_68
Download citation
DOI: https://doi.org/10.1007/978-3-030-27378-1_68
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-27377-4
Online ISBN: 978-3-030-27378-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)