Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage.

Xia Y, Zhang Y, Du Y, Wang Z, Cheng L, Du Z

Journal of nanobiotechnology9 May 2024Cited by 46 (Europe PMC)

PMID38725011PMCIDPMC11080212DOI10.1186/s12951-024-02503-7PepBankPUB-38725011

Summary

BackgroundDry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by a vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the ocular surface, all of which lead to DED deterioration and impair the patients' quality of life and social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such drugs are associated with side effects. The bioavailability of ocular drugs is less than 5% owing to factors such as rapid tear turnover and the presence of the corneal barrier. This calls for investigations to overcome these challenges associated with ocular drug administration.ResultsA novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study. In terms of delivery, PHP-DPS@INS nanoparticles (NPs) overcame the ocular surface transport barrier by adopting the strategy of "ocular surface electrostatic adhesion-lysosomal site-directed escape". In terms of therapy, PHP-DPS@INS achieved mitochondrial targeting and antioxidant effects through SS-31 peptide, and exerted an anti-inflammatory effect by loading insulin to reduce mitochondrial inflammatory metabolites. Ultimately, the synergistic action of "anti-inflammation-antioxidation-mitochondrial function restoration" breaks the vicious cycle associated with DED. The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro. Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1β, IL-6, and TNF-α). Additionally, PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production and facilitated mitochondrial structural repair. In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability. It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice. Moreover, it demonstrated favorable safety profiles both in vitro and in vivo.ConclusionIn summary, this study successfully developed a comprehensive DED management nanosystem that overcame the ocular surface transmission barrier and disrupted the vicious cycle that lead to dry eye pathogenesis. Additionally, it pioneered the regulation of mitochondrial metabolites as an anti-inflammatory treatment for ocular conditions, presenting a safe, efficient, and innovative therapeutic strategy for DED and other inflammatory diseases.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone10

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

01AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Pharmacokinetics
In dry eye disease mice, PHP-DPS@INS enhanced the adhesion duration and corneal permeability of the ocular surface, improving insulin bioavailability.
In plain wordsIn dry eye mice, a nanoparticle carrying SS‑31 and insulin stayed longer on the eye and passed the cornea better.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseOcular surface adhesion duration and corneal permeability
Study
mousen: not reported in source
Dry eye disease mice
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
In vivo, the PHP-DPS@INS treatment significantly enhanced the adhesion duration and corneal permeability of the ocular surface in DED mice, thereby improving insulin bioavailability.
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501106
02AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In dry eye disease mice, PHP-DPS@INS restored tear secretion.
In plain wordsIn dry eye mice, a nanoparticle carrying SS‑31 and insulin restored tear production.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseTear secretion
Study
mousen: not reported in source
Dry eye disease mice
Outcome group
Ocular surface · Eye
Source sentences
Summary
It also restored tear secretion, suppressed ocular surface damage, and reduced inflammation in DED mice.
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501107
03AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In dry eye disease mice, PHP-DPS@INS suppressed ocular surface damage.
In plain wordsIn dry eye mice, a nanoparticle carrying SS‑31 and insulin reduced damage to the eye surface.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseOcular surface damage
Study
mousen: not reported in source
Dry eye disease mice
Outcome group
Ocular surface · Eye
Source sentences
Summary
suppressed ocular surface damage, and reduced inflammation in DED mice.
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501108
04AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In dry eye disease mice, PHP-DPS@INS reduced inflammation.
In plain wordsIn dry eye mice, a nanoparticle carrying SS‑31 and insulin reduced eye inflammation.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseOcular inflammation
Study
mousen: not reported in source
Dry eye disease mice
Outcome group
Inflammation markers · Immune and inflammation
Source sentences
Summary
and reduced inflammation in DED mice.
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501109
05AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Safety outcome
PHP-DPS@INS showed favorable safety profiles both in vitro and in vivo.
In plain wordsA nanoparticle carrying SS‑31 and insulin showed good safety in cell and mouse tests.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeSafety profile in vitro and in vivo
Study
mousen: not reported in source
Dry eye disease mice
Outcome group
Adverse events · Whole body
Source sentences
Summary
Moreover, it demonstrated favorable safety profiles both in vitro and in vivo.
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501110
06LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Activity measurement
In vitro, the SS‑31 and insulin liposome nanosystem PHP-DPS@INS showed remarkable cellular uptake, lysosomal escape and mitochondrial targeting.
In plain wordsIn lab tests, a nanoparticle carrying SS‑31 and insulin entered cells and reached mitochondria well.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseCellular uptake, lysosomal escape and mitochondrial targeting
Study
n: not reported in source
In vitro dry eye models
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
The PHP-DPS@INS demonstrated remarkable cellular uptake, lysosomal escape, and mitochondrial targeting in vitro.
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501101
07LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Mechanism
In an in vitro hypertonic model of dry eye, PHP-DPS@INS normalized the elevated level of mitochondrial fumarate.
In plain wordsIn lab tests, a nanoparticle carrying SS‑31 and insulin brought a raised inflammation-linked metabolite back to normal.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial fumarate
Study
n: not reported in source
In vitro dry eye models
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1β, IL-6, and TNF-α).
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501102
08LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Efficacy outcome
In an in vitro hypertonic model of dry eye, PHP-DPS@INS reduced the levels of IL-1β, IL-6 and TNF-α.
In plain wordsIn lab tests, a nanoparticle carrying SS‑31 and insulin lowered levels of three inflammation signals.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIL-1b, IL-6 and TNF-a levels
Study
n: not reported in source
In vitro dry eye models
Outcome group
Inflammation markers · Immune and inflammation
Source sentences
Summary
Targeted metabolomics analysis revealed that PHP-DPS@INS effectively normalized the elevated level of mitochondrial proinflammatory metabolite fumarate in an in vitro hypertonic model of DED, thereby reducing the levels of key inflammatory factors (IL-1β, IL-6, and TNF-α).
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501103
09LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Efficacy outcome
In vitro, PHP-DPS@INS strongly inhibited reactive oxygen species production.
In plain wordsIn lab tests, a nanoparticle carrying SS‑31 and insulin strongly reduced harmful oxygen molecules.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseReactive oxygen species production
Study
n: not reported in source
In vitro dry eye models
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
PHP-DPS@INS strongly inhibited reactive oxygen species (ROS) production
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501104
10LabNot a test of Elamipretide (SS-31) aloneIn vitro (cells)Efficacy outcome
In vitro, PHP-DPS@INS facilitated mitochondrial structural repair.
In plain wordsIn lab tests, a nanoparticle carrying SS‑31 and insulin helped repair mitochondria structure.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial structural repair
Study
n: not reported in source
In vitro dry eye models
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
and facilitated mitochondrial structural repair.
1 context sentence(design, population, supporting numbers)
Summary · context
A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed in this study.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3872501105

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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