PMID- 37075118
OWN - NLM
STAT- MEDLINE
DCOM- 20230421
LR  - 20230422
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 9
IP  - 16
DP  - 2023 Apr 21
TI  - Matrix metalloproteinase-3 (MMP-3)-mediated gene therapy for glaucoma.
PG  - eadf6537
LID - 10.1126/sciadv.adf6537 [doi]
LID - eadf6537
AB  - Approximately 80 million people globally are affected by glaucoma, with a 
      projected increase to over 110 million by 2040. Substantial issues surrounding 
      patient compliance remain with topical eye drops, and up to 10% of patients 
      become treatment resistant, putting them at risk of permanent vision loss. The 
      major risk factor for glaucoma is elevated intraocular pressure, which is 
      regulated by the balance between the secretion of aqueous humor and the 
      resistance to its flow across the conventional outflow pathway. Here, we show 
      that adeno-associated virus 9 (AAV9)-mediated expression of matrix 
      metalloproteinase-3 (MMP-3) can increase outflow in two murine models of glaucoma 
      and in nonhuman primates. We show that long-term AAV9 transduction of the corneal 
      endothelium in the nonhuman primate is safe and well tolerated. Last, MMP-3 
      increases outflow in donor human eyes. Collectively, our data suggest that 
      glaucoma can be readily treated with gene therapy-based methods, paving the way 
      for deployment in clinical trials.
FAU - O'Callaghan, Jeffrey
AU  - O'Callaghan J
AUID- ORCID: 0000-0001-8818-4331
AD  - Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
FAU - Delaney, Conor
AU  - Delaney C
AUID- ORCID: 0000-0001-8735-2225
AD  - Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
FAU - O'Connor, Merissa
AU  - O'Connor M
AD  - Virscio Inc., New Haven, CT, USA.
FAU - van Batenburg-Sherwood, Joseph
AU  - van Batenburg-Sherwood J
AUID- ORCID: 0000-0002-4402-9767
AD  - Department of Bioengineering, Imperial College London, London, UK.
FAU - Schicht, Martin
AU  - Schicht M
AUID- ORCID: 0000-0001-5155-5477
AD  - Institute of Functional and Clinical Anatomy, University of Erlangen-Nuremburg, 
      Erlangen, Germany.
FAU - Lutjen-Drecoll, Elke
AU  - Lutjen-Drecoll E
AD  - Institute of Functional and Clinical Anatomy, University of Erlangen-Nuremburg, 
      Erlangen, Germany.
FAU - Hudson, Natalie
AU  - Hudson N
AD  - Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
FAU - Ni Dhubhghaill, Sorcha
AU  - Ni Dhubhghaill S
AUID- ORCID: 0000-0002-1115-7834
AD  - Department of Ophthalmology, Antwerp University Hospital (UZA), Edegem, Belgium.
FAU - Humphries, Peter
AU  - Humphries P
AD  - Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
FAU - Stanley, Chris
AU  - Stanley C
AUID- ORCID: 0000-0002-3367-3856
AD  - Virscio Inc., New Haven, CT, USA.
FAU - Keravala, Annahita
AU  - Keravala A
AD  - Exhaura, 10 Earlsfort Terrace, Dublin 2, Ireland.
FAU - Chalberg, Thomas
AU  - Chalberg T
AUID- ORCID: 0000-0001-8653-6735
AD  - Exhaura, 10 Earlsfort Terrace, Dublin 2, Ireland.
FAU - Lawrence, Matthew S
AU  - Lawrence MS
AUID- ORCID: 0000-0002-5931-7390
AD  - Virscio Inc., New Haven, CT, USA.
FAU - Campbell, Matthew
AU  - Campbell M
AUID- ORCID: 0000-0003-3325-240X
AD  - Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
LA  - eng
PT  - Journal Article
DEP - 20230419
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Intraocular Pressure
MH  - Matrix Metalloproteinase 3/metabolism
MH  - *Glaucoma/genetics/therapy/metabolism
MH  - Aqueous Humor/metabolism
MH  - Genetic Therapy
PMC - PMC10115410
EDAT- 2023/04/19 18:42
MHDA- 2023/04/21 06:41
PMCR- 2023/04/19
CRDT- 2023/04/19 14:04
PHST- 2023/04/21 06:41 [medline]
PHST- 2023/04/19 18:42 [pubmed]
PHST- 2023/04/19 14:04 [entrez]
PHST- 2023/04/19 00:00 [pmc-release]
AID - adf6537 [pii]
AID - 10.1126/sciadv.adf6537 [doi]
PST - ppublish
SO  - Sci Adv. 2023 Apr 21;9(16):eadf6537. doi: 10.1126/sciadv.adf6537. Epub 2023 Apr 
      19.