{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T06:13:41Z","timestamp":1768716821229,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T00:00:00Z","timestamp":1662163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Arkansas for Medical Sciences and the Pat and Willard Walker Eye Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is an eye disease that can cause central vision loss, particularly in the elderly population. There are 2 classes of AMD, wet-type and dry-type. Wet-type involves excess angiogenesis around the macula, referred to as choroidal neovascularization (CNV). This can result in leaky vessels, often causing more severe vision loss than dry-type AMD. Adiponectin peptide 1 (APNp1) has been shown to slow the progression of CNV. Here, we used a mouse model and FITC-labeled APNp1 to determine if APNp1 could be delivered effectively as an eye drop. Our experiment revealed that topically applied FITC-APNp1 could reach the macula of the eye, which is crucial for treating wet-type AMD. We also tested delivery of APNp1 via injection of an adeno-associated virus (AAV) vector in a mouse model of CNV. AAV is a harmless virus easy to manipulate and is very often used for protein or peptide deliveries. Results revealed an increase in the expression of APNp1 in the retina and choroid over a 28-day period. Finally, we investigated the mechanism by which APNp1 affects CNV by examining the expression of adiponectin receptor 1 (AdipoR1) and proliferating cell nuclear antigen (PCNA) in the retinal and choroidal tissue of the mouse eyes. AdipoR1 and PCNA were overexpressed in these tissues in mice with laser-induced CNV compared to na\u00efve mice. Based on our data shown here, we think it will enhance our understanding of APNp1 as a therapeutic agent for wet-type AMD and possible treatment alternatives that could be more beneficial for patients.<\/jats:p>","DOI":"10.3390\/biom12091232","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T20:48:25Z","timestamp":1662410905000},"page":"1232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Role of Adiponectin Peptide I (APNp1) in Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"12","author":[{"given":"Connor","family":"Logan","sequence":"first","affiliation":[{"name":"Pat & Willard Walker Eye Research Center, Jones Eye Institute, Department of Ophthalmology, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriy","family":"Lyzogubov","sequence":"additional","affiliation":[{"name":"Pat & Willard Walker Eye Research Center, Jones Eye Institute, Department of Ophthalmology, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nalini","family":"Bora","sequence":"additional","affiliation":[{"name":"Pat & Willard Walker Eye Research Center, Jones Eye Institute, Department of Ophthalmology, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4781-1217","authenticated-orcid":false,"given":"Puran","family":"Bora","sequence":"additional","affiliation":[{"name":"Pat & Willard Walker Eye Research Center, Jones Eye Institute, Department of Ophthalmology, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/archopht.122.4.564","article-title":"Prevalence of age-related macular degeneration in the United States","volume":"122","author":"Friedman","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/S0140-6736(08)61759-6","article-title":"Age-related macular degeneration","volume":"372","author":"Coleman","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1080\/07853890600946724","article-title":"Age-related macular degeneration--emerging pathogenetic and therapeutic concepts","volume":"38","author":"Gehrs","year":"2006","journal-title":"Ann. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"221","DOI":"10.2174\/138945011794182755","article-title":"Age related macular degeneration and visual disability","volume":"12","author":"Christoforidis","year":"2011","journal-title":"Curr. Drug Targets"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1001\/archophthalmol.2009.58","article-title":"Forecasting age-related macular degeneration through the year 2050: The potential impact of new treatments","volume":"127","author":"Rein","year":"2009","journal-title":"Arch. Ophthalmol."},{"key":"ref_7","unstructured":"Kolb, H., Fernandez, E., and Nelson, R. (2008). Age-Related Macular Degeneration (AMD). Webvision: The Organization of the Retina and Visual System, John A. Moran Eye Center."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1056\/NEJMra062326","article-title":"Age-related macular degeneration","volume":"355","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ajo.2018.10.022","article-title":"Validated prediction models for macular degeneration progression and predictors of visual acuity loss identify high-risk individuals","volume":"198","author":"Seddon","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00420-018-1355-y","article-title":"Macular degeneration and occupational risk factors: A systematic review","volume":"92","author":"Modenese","year":"2019","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1001\/jamaophthalmol.2016.5314","article-title":"The potential importance of detection of neovascular age-related macular degeneration when visual acuity is relatively good","volume":"135","author":"Ho","year":"2017","journal-title":"JAMA Opthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ophtha.2018.07.028","article-title":"Safety and efficacy of anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration: A report by the American Academy of Ophthalmology","volume":"126","author":"Bakri","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_13","first-page":"172","article-title":"Review of Neovascular Age-Related Macular Degeneration Treatment Options","volume":"25","author":"Holekamp","year":"2019","journal-title":"Am. J. Manag. Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0896-1549(01)00009-8","article-title":"Mechanisms of age-related macular degeneration","volume":"15","author":"Husain","year":"2002","journal-title":"Ophthalmol. Clin. N. Am."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1177\/0300985809359598","article-title":"Animals as models of age-related macular degeneration: An imperfect measure of the truth","volume":"47","author":"Zeiss","year":"2010","journal-title":"Vet. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.bbamcr.2012.05.017","article-title":"Inhibitory role of adiponectin peptide I on rat choroidal neovascularization","volume":"1823","author":"Lyzogubov","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16229","DOI":"10.1074\/jbc.M110.204701","article-title":"Polyethylene glycol (PEG)-induced mouse model of choroidal neovascularization","volume":"286","author":"Lyzogubov","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"491","DOI":"10.4049\/jimmunol.174.1.491","article-title":"Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization","volume":"174","author":"Bora","year":"2005","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.4049\/jimmunol.177.3.1872","article-title":"Complement activation via alternative pathway is critical in the development of laser-induced choroidal neovascularization: Role of factor B and factor H","volume":"177","author":"Bora","year":"2006","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/j.febslet.2007.04.024","article-title":"Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin","volume":"581","author":"Bora","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_21","first-page":"488","article-title":"Proliferation of CECs requires dual signaling through both MAPK\/ERK and PI 3-K\/Akt pathways","volume":"42","author":"Zubilewicz","year":"2001","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1101\/sqb.2012.76.010587","article-title":"Adiponectin, adiponectin receptors, and epigenetic regulation of adipogenesis","volume":"76","author":"Kadowaki","year":"2011","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.neulet.2012.02.050","article-title":"Adiponectin receptor 1 gene (ADIPOR1) variant is associated with advanced age-related macular degeneration in Finnish population","volume":"513","author":"Kaarniranta","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1007\/s00125-012-2598-x","article-title":"Adiponectin: Mechanistic insights and clinical implications","volume":"55","author":"Turer","year":"2012","journal-title":"Diabetologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10549-007-9874-3","article-title":"Growth-inhibitory effect of adiponectin via adiponectin receptor 1 on human breast cancer cells through inhibition of S-phase entry without inducing apoptosis","volume":"112","author":"Nakayama","year":"2008","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.mce.2008.01.023","article-title":"Globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation","volume":"285","author":"Ogunwobi","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.peptides.2012.11.017","article-title":"Adipokine adiponectin is a potential protector to human bronchial epithelial cell for regulating proliferation, wound repair and apoptosis: Comparison with leptin and resistin","volume":"40","author":"Zhu","year":"2013","journal-title":"Peptides"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1007\/s00239-004-0375-2","article-title":"PAQR proteins: A novel membrane receptor family defined by an ancient 7-transmembrane pass motif","volume":"61","author":"Tang","year":"2005","journal-title":"J. Mol. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5231","DOI":"10.1210\/en.2012-1368","article-title":"Overexpression of the adiponectin receptor AdipoR1 in rat skeletal muscle amplifies local insulin sensitivity","volume":"153","author":"Patel","year":"2012","journal-title":"Endocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1515\/bc.2010.104","article-title":"Molecular mechanisms of signal transduction via adiponectin and adiponectin receptors","volume":"391","author":"Heiker","year":"2010","journal-title":"Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1111\/j.1349-7006.2007.00486.x","article-title":"Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2","volume":"98","author":"Ishikawa","year":"2007","journal-title":"Cancer Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/019262339802600121","article-title":"The C3(1)\/SV40 T antigen transgenic mouse model of prostate and mammary cancer","volume":"26","author":"Shibata","year":"1998","journal-title":"Toxicol. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"202","DOI":"10.2169\/internalmedicine.38.202","article-title":"Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity","volume":"38","author":"Funahashi","year":"1999","journal-title":"Intern. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nature01705","article-title":"Cloning of adiponectin receptors that mediate antidiabetic metabolic effects","volume":"423","author":"Yamauchi","year":"2003","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/1756-9966-30-107","article-title":"Adiponectin receptor-1 expression is associated with good prognosis in gastric cancer","volume":"30","author":"Tsukada","year":"2011","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1042\/CBI20090013","article-title":"Expression and role of adiponectin receptor 1 in lipopolysaccharide-induced proliferation of cultured rat adventitial fibroblasts","volume":"34","author":"Cai","year":"2010","journal-title":"Cell Biol. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1093\/humrep\/dep292","article-title":"Role of adiponectin receptors, AdipoR1 and AdipoR2, in the steroidogenesis of the human granulosa tumor cell line, KGN","volume":"24","author":"Pierre","year":"2009","journal-title":"Hum. Reprod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1359\/jbmr.090227","article-title":"Development of arterial calcification in adiponectin-deficient mice: Adiponectin regulates arterial calcification","volume":"24","author":"Luo","year":"2009","journal-title":"J. Bone Min. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11682","DOI":"10.1021\/bi801451f","article-title":"The adiponectin receptors AdipoR1 and AdipoR2 activate ERK1\/2 through a Src\/Ras-dependent pathway and stimulate cell growth","volume":"47","author":"Lee","year":"2008","journal-title":"Biochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1038\/nature08991","article-title":"Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca2+ and AMPK\/SIRT1","volume":"464","author":"Iwabu","year":"2010","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/nm1557","article-title":"Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions","volume":"13","author":"Yamauchi","year":"2007","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kanazawa, I., Yamaguchi, T., Yano, S., Yamauchi, M., Yamamoto, M., and Sugimoto, T. (2007). Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. BMC Cell Biol., 8.","DOI":"10.1186\/1471-2121-8-51"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1136\/bjo.2011.204685","article-title":"Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation","volume":"96","author":"Gasperini","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1097\/IAE.0b013e3181a2c1c3","article-title":"Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration","volume":"29","author":"Forooghian","year":"2009","journal-title":"Retina"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1167\/iovs.09-4065","article-title":"Alterations in the intraocular cytokine milieu after intravitreal bevacizumab","volume":"51","author":"Forooghian","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.ymthe.2005.04.022","article-title":"Lont term evaluation of AAV mediated sFlt-1 gene therapy for ocular neovascularization in mice and monkeys","volume":"12","author":"Lai","year":"2005","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.exer.2010.01.011","article-title":"Self- complementary AAV5 vector facilitates quicker transgene expression in photoreceptor and retinal epithelial cells of normal mouse","volume":"90","author":"Kong","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/jgm.1126","article-title":"Novel AAV serotypes for improved ocular gene transfer","volume":"10","author":"Lebherz","year":"2008","journal-title":"J. Gene Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1073\/pnas.0438014100","article-title":"Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration","volume":"100","author":"Bora","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/9\/1232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:23:02Z","timestamp":1760142182000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/9\/1232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,3]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["biom12091232"],"URL":"https:\/\/doi.org\/10.3390\/biom12091232","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,3]]}}}