PMID- 35203674
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220401
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 10
IP  - 2
DP  - 2022 Feb 16
TI  - Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic 
      Retinopathy in an Experimental Model.
LID - 10.3390/biomedicines10020465 [doi]
LID - 465
AB  - The neurovascular unit (NVU) plays an essential role in the development of 
      diabetic retinopathy (DR). We previously reported that the topical administration 
      (eye drops) of sitagliptin and saxagliptin, two dipeptidyl peptidase-4 inhibitors 
      (DPP-4i), prevents retinal neurodegeneration and vascular leakage in db/db mice. 
      The aim of the present study is to evaluate the minimum effective dose of the 
      topical administration of these DPP-4i. For this purpose, sitagliptin and 
      saxagliptin were tested at different concentrations (sitagliptin: 1 mg/mL, 5 and 
      10 mg/mL, twice per day; saxagliptin: 1 and 10 mg/mL, once or twice per day) in 
      db/db mice. As end points of efficacy, the hallmarks of NVU impairment were 
      evaluated: reactive gliosis, neural apoptosis, and vascular leakage. These 
      parameters were assessed by immunohistochemistry, cell counting, and the Evans 
      blue method, respectively. Our results demonstrated that the minimum effective 
      dose is 5 mg/mL twice per day for sitagliptin, and 10 mg/mL twice per day for 
      saxagliptin. In conclusion, this study provides useful results for the design of 
      future preclinical regulatory studies and for planning clinical trials.
FAU - Bogdanov, Patricia
AU  - Bogdanov P
AUID- ORCID: 0000-0003-0669-4958
AD  - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, 08035 
      Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas 
      Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, 
      Spain.
FAU - Ramos, Hugo
AU  - Ramos H
AUID- ORCID: 0000-0001-6443-7576
AD  - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, 08035 
      Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas 
      Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, 
      Spain.
FAU - Valeri, Marta
AU  - Valeri M
AD  - Unit of High Technology, Vall d'Hebron Research Institute, 08035 Barcelona, 
      Spain.
FAU - Deas-Just, Anna
AU  - Deas-Just A
AUID- ORCID: 0000-0002-3129-6313
AD  - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, 08035 
      Barcelona, Spain.
FAU - Huerta, Jordi
AU  - Huerta J
AUID- ORCID: 0000-0002-9908-8051
AD  - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, 08035 
      Barcelona, Spain.
FAU - Simo, Rafael
AU  - Simo R
AUID- ORCID: 0000-0003-0475-3096
AD  - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, 08035 
      Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas 
      Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, 
      Spain.
AD  - Department of Medicine, Universitat Autonoma de Barcelona, 08193 Barcelona, 
      Spain.
FAU - Hernandez, Cristina
AU  - Hernandez C
AUID- ORCID: 0000-0002-3109-1721
AD  - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, 08035 
      Barcelona, Spain.
AD  - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas 
      Asociadas (CIBERDEM), Instituto de Salud Carlos III (ICSIII), 28029 Madrid, 
      Spain.
AD  - Department of Medicine, Universitat Autonoma de Barcelona, 08193 Barcelona, 
      Spain.
LA  - eng
GR  - PID2019-104225RB-I00/Ministerio de Economia y Competitividad/
GR  - DTS18/0163, PI19/01215 and ICI20/00129/Instituto de Salud Carlos III/
PT  - Journal Article
DEP - 20220216
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC8962353
OTO - NOTNLM
OT  - db/db mice
OT  - diabetic retinopathy
OT  - dipeptidyl peptidase-4 inhibitors
OT  - experimental diabetes
OT  - neurovascular unit
OT  - retinal neurodegeneration
OT  - saxagliptin
OT  - sitagliptin
COIS- The authors declare no conflict of interest. Vall d'Hebron Research Institute 
      holds intellectual property related to the use of ocular DPP-4 inhibitors to 
      treat diabetic retinopathy. No other potential conflict of interest relevant to 
      this article were reported.
EDAT- 2022/02/26 06:00
MHDA- 2022/02/26 06:01
PMCR- 2022/02/16
CRDT- 2022/02/25 01:02
PHST- 2022/01/14 00:00 [received]
PHST- 2022/02/11 00:00 [revised]
PHST- 2022/02/13 00:00 [accepted]
PHST- 2022/02/25 01:02 [entrez]
PHST- 2022/02/26 06:00 [pubmed]
PHST- 2022/02/26 06:01 [medline]
PHST- 2022/02/16 00:00 [pmc-release]
AID - biomedicines10020465 [pii]
AID - biomedicines-10-00465 [pii]
AID - 10.3390/biomedicines10020465 [doi]
PST - epublish
SO  - Biomedicines. 2022 Feb 16;10(2):465. doi: 10.3390/biomedicines10020465.