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According to the level of microvascular degeneration and ischemic damage, DR is classified into non-proliferative DR (NPDR), and end-stage, proliferative DR (PDR). Despite advances in the disease etiology and pathogenesis, molecular understanding of end-stage PDR, characterized by ischemia- and inflammation-associated neovascularization and fibrosis, remains incomplete due to the limited availability of ideal clinical samples and experimental research models. Since a great portion of patients do not benefit from current treatments, improved therapies are essential. DR is known to be a complex and multifactorial disease featuring the interplay of microvascular, neurodegenerative, metabolic, genetic\/epigenetic, immunological, and inflammation-related factors. Particularly, deeper knowledge on the mechanisms and pathophysiology of most advanced PDR is critical. Lymphatic-like vessel formation coupled with abnormal endothelial differentiation and progenitor cell involvement in the neovascularization associated with PDR are novel recent findings which hold potential for improved DR treatment. Understanding the underlying mechanisms of PDR pathogenesis is therefore crucial. To this goal, multidisciplinary approaches and new ex vivo models have been developed for a more comprehensive molecular, cellular and tissue-level understanding of the disease. This is the first step to gain the needed information on how PDR can be better evaluated, stratified, and treated.<\/jats:p>","DOI":"10.3390\/ijms19124034","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T03:58:17Z","timestamp":1544759897000},"page":"4034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Lymphatic Vascular Structures: A New Aspect in Proliferative Diabetic Retinopathy"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4481-8798","authenticated-orcid":false,"given":"Erika","family":"Gucciardo","sequence":"first","affiliation":[{"name":"Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirpa","family":"Loukovaara","sequence":"additional","affiliation":[{"name":"Unit of Vitreoretinal Surgery, Ophthalmology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petri","family":"Salven","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9110-8719","authenticated-orcid":false,"given":"Kaisa","family":"Lehti","sequence":"additional","affiliation":[{"name":"Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland"},{"name":"Department of Microbiology, Tumor, and Cell Biology (MTC), Karolinska Institutet, SE-17165 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. 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