Ocular Nanoparticle Toxicity and Transfection of the Retina and Retinal Pigment Epithelium
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Chitosan, PCEP (poly{[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium iodide] ethyl phosphate}), and magnetic nanoparticles (MNPs) were evaluated for the safe delivery of genes in the eye. Rabbits were injected with nanoparticles either intravitreally (IV) or subretinally (SR) and sacrificed 7 days later. Eyes were grossly evaluated for retinal pigment epithelium abnormalities, retinal degeneration, and inflammation. All eyes were cryopreserved and sectioned for analysis of toxicity and expression of either enhanced green or red fluorescent proteins. All of the nanoparticles were able to transfect cells in vitro and in vivo. IV chitosan showed inflammation in 12/13 eyes, whereas IV PCEP and IV MNPs were not inflammatory and did not induce retinal pathology. SR PCEP was nontoxic in the majority of cases but yielded poor transfection, whereas SR MNPs were nontoxic and yielded good transfection. Therefore, we conclude that the best nanoparticle evaluated in vivo was the least toxic nanoparticle tested, the MNP.
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In rabbits receiving CHI, PCEP, or MNP vectors, inflammatory cell infiltration and retinal degeneration were observed with CHI but not with the others.
“Inflammatory cell infiltration and retinal degeneration were observed in the rabbits that received the CHI vector but not the others.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [75]
Immunolabelling revealed that neither CHI nor PCEP were able to transfect ocular cells efficiently.
“Further, immunolabelling revealed that neither CHI nor PCEP were able to transfect ocular cells efficiently.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [75]
Neither PCEP nor MNP induced inflammatory cell infiltration in both intravitreal and subretinal injection, while retinal degeneration was observed in 15% of eyes that received PCEP subretinally.
“Neither PCEP nor MNP induced inflammatory cell infiltration in both ways of injection, while retinal degeneration was observed in 15% of the eyes that received PCEP subretinally.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [75]
Non-viral vectors not only lack efficiency for ocular delivery applications but can also induce immune responses.
“These results further reiterate that non-viral vectors not only lack efficiency for ocular delivery applications but can also induce immune responses [75].”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [75]
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- Authors
- Prow, T. W., Bhutto, I., Kim, S. Y., Grebe, R., Merges, C., McLeod, D. S., Uno, K., Mennon, M., Rodriguez, L., Leong, K., & Lutty, G. A.
- Affiliations
- Johns Hopkins University (US)
- United States Food and Drug Administration (US)
- Duke University (US)
- Corresponding author
- Lutty, Gerard A.
- Venue
- Nanomedicine: Nanotechnology, Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 4
- Issue
- 4
- Pages
- 340-349
- ISSN
- 1549-9634 (ISSN-L)
- PMC
- PMC4818568
- OpenAlex
- W1967087156
- Cited by
- 111
- References
- 17
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 6 · 2013: 10 · 2012: 13
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nanomedicine Nanotechnology Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007525)
- National Eye Institute (R01EY016151, R01-EY09357, L40 EY016943, #EY01765, R03EY013744, P30EY001765, R01EY009357)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- retinal pigment epithelium, chitosan, PCEP, magnetic nanoparticles, intravitreal injection, subretinal injection, retinal inflammation, retinal degeneration, fluorescent protein expression
- MeSH terms
- Animals, Eye, Immunohistochemistry, Polymers, Rabbits, Retina, Transfection, Microscopy, Immunoelectron, Microscopy, Confocal, Microscopy, Electron, Transmission, Chitosan, Green Fluorescent Proteins, Nanoparticles, Retinal Pigment Epithelium
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