Tear Film and Keratitis in Space: Fluid Dynamics and Nanomedicine Strategies for Ocular Protection in Microgravity
Abstract
1. Introduction
2. Fluid Dynamics in Spaceflight
2.1. Navier–Stokes in Microgravity
- v: velocity field of the tear film
- ρ: density of the tears
- μ: dynamic viscosity
- ∇p: pressure gradient (reduced in microgravity)
- fsurfacetension: capillary force at fluid interfaces
2.2. Capillary Number
- μ: dynamic viscosity
- U: characteristic velocity (e.g., blink-induced tear motion)
- γ: surface tension
2.3. Bond Number
- Δρ: density difference between tears and air
- g: gravitational acceleration (approaches zero in space)
- L: characteristic length scale (e.g., tear meniscus height)
- γ: surface tension
2.4. Immune Dysregulation and Risk of Infection in Microgravity
2.5. Impact on Mission
3. Keratitis in Spaceflight
- a.
- Viral Keratitis
- b.
- Bacterial Keratitis
- c.
- Fungal Keratitis
4. Nanomedicine
- a.
- Dry Eye Syndrome
- b.
- Keratitis
- c.
- Spaceflight Associated Neuro–Ocular Syndrome
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
SADES | Spaceflight-Associated Dry Eye Syndrome |
SANS | Spaceflight-Associated Neuro–ocular Syndrome |
IFNγ | Interferon Gamma |
IL-10 | Interleukin-10 |
IL-17A | Interleukin-17A |
NK cells | Natural Killer Cells |
NF-κB | Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells |
ROS | Reactive Oxygen Species |
NLCs | Nanostructured Lipid Carriers |
ELR | Elastin-Like Recombinamer |
SAS | Supercritical Antisolvent (technique) |
PLGA | Poly(lactic-co-glycolic acid) |
References
- Rolando, M.; Zierhut, M. The Ocular Surface and Tear Film and Their Dysfunction in Dry Eye Disease. Surv. Ophthalmol. 2001, 45, S203–S210. [Google Scholar] [CrossRef] [PubMed]
- Roy, N.S.; Wei, Y.; Ying, G.-S.; Maguire, M.G.; Asbell, P.A. Association of Tear Cytokine Concentrations with Symptoms and Signs of Dry Eye Disease: Baseline Data from the Dry Eye Assessment and Management (DREAM) Study. Curr. Eye Res. 2023, 48, 339–347. [Google Scholar] [CrossRef] [PubMed]
- Foldager, N.; Andersen, T.A.; Jessen, F.B.; Ellegaard, P.; Stadeager, C.; Videbaek, R.; Norsk, P. Central Venous Pressure in Humans during Microgravity. J. Appl. Physiol. 1996, 81, 408–412. [Google Scholar] [CrossRef]
- Afshinnekoo, E.; Scott, R.T.; MacKay, M.J.; Pariset, E.; Cekanaviciute, E.; Barker, R.; Gilroy, S.; Hassane, D.; Smith, S.M.; Zwart, S.R.; et al. Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration. Cell 2020, 183, 1162–1184. [Google Scholar] [CrossRef]
- Lee, A.G.; Mader, T.H.; Gibson, C.R.; Tarver, W.; Rabiei, P.; Riascos, R.F.; Galdamez, L.A.; Brunstetter, T. Spaceflight Associated Neuro-Ocular Syndrome (SANS) and the Neuro-Ophthalmologic Effects of Microgravity: A Review and an Update. npj Microgravity 2020, 6, 7. [Google Scholar] [CrossRef]
- Lee, R.; Ong, J.; Waisberg, E.; Lee, A.G. Corneal Wound Healing in Spaceflight: Implications of Microgravity-Induced Molecular Signaling Modulations for Corneal Health. Eye 2024, 38, 2851–2853. [Google Scholar] [CrossRef]
- Panzo, N.; Memon, H.; Ong, J.; Suh, A.; Sampige, R.; Lee, R.; Waisberg, E.; Kadipasaoglu, C.M.; Berdahl, J.; Chévez-Barrios, P.; et al. Molecular and Biomechanical Changes of the Cornea and Lens in Spaceflight. Life Sci. Space Res. 2025, 45, 151–157. [Google Scholar] [CrossRef]
- Akiyama, T.; Horie, K.; Hinoi, E.; Hiraiwa, M.; Kato, A.; Maekawa, Y.; Takahashi, A.; Furukawa, S. How Does Spaceflight Affect the Acquired Immune System? npj Microgravity 2020, 6, 14. [Google Scholar] [CrossRef]
- Lee, R.; Ong, J.; Waisberg, E.; Mader, T.; Berdahl, J.; Suh, A.; Panzo, N.; Memon, H.; Sampige, R.; Katsev, B.; et al. Potential Risks of Ocular Molecular and Cellular Changes in Spaceflight. Semin. Ophthalmol. 2025, 1–11. [Google Scholar] [CrossRef]
- He, Y.; Northrup, H.; Le, H.; Cheung, A.K.; Berceli, S.A.; Shiu, Y.T. Medical Image-Based Computational Fluid Dynamics and Fluid-Structure Interaction Analysis in Vascular Diseases. Front. Bioeng. Biotechnol. 2022, 10, 855791. [Google Scholar] [CrossRef]
- Langbein, D. Fluid Statics and Dynamics in Microgravity. J. Phys. Condens. Matter 1990, 2, SA491–SA498. [Google Scholar] [CrossRef]
- Talbott, K.; Xu, A.; Anderson, D.M.; Seshaiyer, P. Modelling the Evaporation of a Tear Film over a Contact Lens. Math. Med. Biol. A J. IMA 2015, 32, 209–238. [Google Scholar] [CrossRef] [PubMed]
- Tiffany, J.M.; Winter, N.; Bliss, G. Tear Film Stability and Tear Surface Tension. Curr. Eye Res. 1989, 8, 507–515. [Google Scholar] [CrossRef]
- Creech, J.L.; Do, L.T.; Fatt, I.; Radke, C.J. In Vivo Tear-Film Thickness Determination and Implications for Tear-Film Stability. Curr. Eye Res. 1998, 17, 1058–1066. [Google Scholar] [CrossRef]
- Wong, H.; Fatt, I.; Radke, C.J. Deposition and Thinning of the Human Tear Film. J. Colloid Interface Sci. 1996, 184, 44–51. [Google Scholar] [CrossRef]
- Xu, X.; Li, G.; Zuo, Y.Y. Biophysical Properties of Tear Film Lipid Layer I. Surface Tension and Surface Rheology. Biophys. J. 2022, 121, 439–450. [Google Scholar] [CrossRef]
- Sahlin, S.; Chen, E. Gravity, Blink Rate, and Lacrimal Drainage Capacity. Am. J. Ophthalmol. 1997, 124, 758–764. [Google Scholar] [CrossRef]
- Maurice, D.M. The Dynamics and Drainage of Tears. Int. Ophthalmol. Clin. 1973, 13, 103. [Google Scholar] [CrossRef]
- Lee, R.; Ong, J.; Waisberg, E.; Lee, A.G. Spaceflight Associated Dry Eye Syndrome (SADES): Radiation, Stressors, and Ocular Surface Health. Life Sci. Space Res. 2024, 43, 75–81. [Google Scholar] [CrossRef]
- Marchal, S.; Choukér, A.; Bereiter-Hahn, J.; Kraus, A.; Grimm, D.; Krüger, M. Challenges for the Human Immune System after Leaving Earth. npj Microgravity 2024, 10, 106. [Google Scholar] [CrossRef]
- Crucian, B.; Babiak-Vazquez, A.; Johnston, S.; Pierson, D.L.; Ott, C.M.; Sams, C. Incidence of Clinical Symptoms during Long-Duration Orbital Spaceflight. Int. J. Gen. Med. 2016, 9, 383–391. [Google Scholar] [CrossRef] [PubMed]
- Kim, J.; Tierney, B.T.; Overbey, E.G.; Dantas, E.; Fuentealba, M.; Park, J.; Narayanan, S.A.; Wu, F.; Najjar, D.; Chin, C.R.; et al. Single-Cell Multi-Ome and Immune Profiles of the Inspiration4 Crew Reveal Conserved, Cell-Type, and Sex-Specific Responses to Spaceflight. Nat. Commun. 2024, 15, 4954. [Google Scholar] [CrossRef] [PubMed]
- Mehta, S.K.; Laudenslager, M.L.; Stowe, R.P.; Crucian, B.E.; Feiveson, A.H.; Sams, C.F.; Pierson, D.L. Latent Virus Reactivation in Astronauts on the International Space Station. NPJ Microgravity 2017, 3, 11. [Google Scholar] [CrossRef] [PubMed]
- Stepp, M.A.; Menko, A.S. Immune Responses to Injury and Their Links to Eye Disease. Transl. Res. 2021, 236, 52–71. [Google Scholar] [CrossRef]
- Dunvald, A.-C.D.; Järvinen, E.; Mortensen, C.; Stage, T.B. Clinical and Molecular Perspectives on Inflammation-Mediated Regulation of Drug Metabolism and Transport. Clin. Pharmacol. Ther. 2022, 112, 277–290. [Google Scholar] [CrossRef]
- Goto, E.; Yagi, Y.; Matsumoto, Y.; Tsubota, K. Impaired Functional Visual Acuity of Dry Eye Patients. Am. J. Ophthalmol. 2002, 133, 181–186. [Google Scholar] [CrossRef]
- Shah, J.; Ong, J.; Lee, R.; Suh, A.; Waisberg, E.; Gibson, C.R.; Berdahl, J.; Mader, T.H. Risk of Permanent Corneal Injury in Microgravity: Spaceflight-Associated Hazards, Challenges to Vision Restoration, and Role of Biotechnology in Long-Term Planetary Missions. Life 2025, 15, 602. [Google Scholar] [CrossRef]
- Barratt, M.R.; Baker, E.S.; Pool, S.L. (Eds.) Principles of Clinical Medicine for Space Flight; Springer New York: New York, NY, USA, 2019; ISBN 978-1-4939-9887-6. [Google Scholar]
- Crucian, B.E.; Choukèr, A.; Simpson, R.J.; Mehta, S.; Marshall, G.; Smith, S.M.; Zwart, S.R.; Heer, M.; Ponomarev, S.; Whitmire, A.; et al. Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions. Front. Immunol. 2018, 9, 1437. [Google Scholar] [CrossRef]
- Cohrs, R.J.; Mehta, S.K.; Schmid, D.S.; Gilden, D.H.; Pierson, D.L. Asymptomatic Reactivation and Shed of Infectious Varicella Zoster Virus in Astronauts. J. Med. Virol. 2008, 80, 1116–1122. [Google Scholar] [CrossRef]
- Rooney, B.V.; Crucian, B.E.; Pierson, D.L.; Laudenslager, M.L.; Mehta, S.K. Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth. Front. Microbiol. 2019, 10, 16. [Google Scholar] [CrossRef]
- Jones, C. Intimate Relationship Between Stress and Human Alpha-Herpes Virus 1 (HSV-1) Reactivation from Latency. Curr. Clin. Microbiol. Rep. 2023, 10, 236–245. [Google Scholar] [CrossRef] [PubMed]
- Jones, B.R. The Clinical Features of Viral Keratitis and a Concept of Their Pathogenesis. Proc. R. Soc. Med. 1958, 51, 917–924. [Google Scholar] [CrossRef] [PubMed]
- Harris, K.D. Herpes Simplex Virus Keratitis. Home Healthc. Now. 2019, 37, 281. [Google Scholar] [CrossRef] [PubMed]
- Pavletić, B.; Runzheimer, K.; Siems, K.; Koch, S.; Cortesão, M.; Ramos-Nascimento, A.; Moeller, R. Spaceflight Virology: What Do We Know about Viral Threats in the Spaceflight Environment? Astrobiology 2022, 22, 210–224. [Google Scholar] [CrossRef]
- Hatami, H.; Ghaffari Jolfayi, A.; Ebrahimi, A.; Golmohammadi, S.; Zangiabadian, M.; Nasiri, M.J. Contact Lens Associated Bacterial Keratitis: Common Organisms, Antibiotic Therapy, and Global Resistance Trends: A Systematic Review. Front. Ophthalmol. 2021, 1. [Google Scholar] [CrossRef]
- Willcox, M.D.P.; Harmis, N.; Cowell, B.A.; Williams, T.; Holden, B.A. Bacterial Interactions with Contact Lenses; Effects of Lens Material, Lens Wear and Microbial Physiology. Biomaterials 2001, 22, 3235–3247. [Google Scholar] [CrossRef]
- Taylor, P.W. Impact of Space Flight on Bacterial Virulence and Antibiotic Susceptibility. IDR 2015, 8, 249–262. [Google Scholar] [CrossRef]
- Cruzat, A.; Witkin, D.; Baniasadi, N.; Zheng, L.; Ciolino, J.B.; Jurkunas, U.V.; Chodosh, J.; Pavan-Langston, D.; Dana, R.; Hamrah, P. Inflammation and the Nervous System: The Connection in the Cornea in Patients with Infectious Keratitis. Investig. Ophthalmol. Vis. Sci. 2011, 52, 5136–5143. [Google Scholar] [CrossRef]
- Lee, R.; Ong, J.; Waisberg, E.; Fanning, S.L.; Lee, A.G. Spaceflight Associated Dry Eye Syndrome (SADES): Outflow Biophysics and Infection Risk. J. Space Saf. Eng. 2025, 43, 75–81. [Google Scholar] [CrossRef]
- Marra, D.; Ferraro, R.; Caserta, S. Biofilm Contamination in Confined Space Stations: Reduction, Coexistence or an Opportunity? Front. Mater. 2024, 11. [Google Scholar] [CrossRef]
- Flores, P.; Luo, J.; Mueller, D.W.; Muecklich, F.; Zea, L. Space Biofilms—An Overview of the Morphology of Pseudomonas Aeruginosa Biofilms Grown on Silicone and Cellulose Membranes on Board the International Space Station. Biofilm 2024, 7, 100182. [Google Scholar] [CrossRef] [PubMed]
- Barrila, J.; Sarker, S.F.; Hansmeier, N.; Yang, S.; Buss, K.; Briones, N.; Park, J.; Davis, R.R.; Forsyth, R.J.; Ott, C.M.; et al. Evaluating the Effect of Spaceflight on the Host–Pathogen Interaction between Human Intestinal Epithelial Cells and Salmonella Typhimurium. NPJ Microgravity 2021, 7, 9. [Google Scholar] [CrossRef] [PubMed]
- Mukherjee, S.; Bassler, B.L. Bacterial Quorum Sensing in Complex and Dynamically Changing Environments. Nat. Rev. Microbiol. 2019, 17, 371–382. [Google Scholar] [CrossRef]
- Liu, C.; Hu, J.; Fang, X.; Zhang, D.; Chang, D.; Wang, J.; Li, T.; Guo, Y.; Dai, W.; Liu, C. Genome Sequence of Pseudomonas Aeruginosa Strain LCT-PA41, with Changed Metabolism after Space Flight. Genome Announc. 2014, 2, e01124-13. [Google Scholar] [CrossRef]
- Morrison, M.D.; Thissen, J.B.; Karouia, F.; Mehta, S.; Urbaniak, C.; Venkateswaran, K.; Smith, D.J.; Jaing, C. Investigation of Spaceflight Induced Changes to Astronaut Microbiomes. Front. Microbiol. 2021, 12, 659179. [Google Scholar] [CrossRef]
- Bharindwal, S.; Goswami, N.; Jha, P.; Pandey, S.; Jobby, R. Prospective Use of Probiotics to Maintain Astronaut Health during Spaceflight. Life 2023, 13, 727. [Google Scholar] [CrossRef]
- Jurkunas, U.; Behlau, I.; Colby, K. Fungal Keratitis: Changing Pathogens and Risk Factors. Cornea 2009, 28, 638. [Google Scholar] [CrossRef]
- Sugita, T.; Yamazaki, T.; Makimura, K.; Cho, O.; Yamada, S.; Ohshima, H.; Mukai, C. Comprehensive Analysis of the Skin Fungal Microbiota of Astronauts during a Half-Year Stay at the International Space Station. Med. Mycol. 2016, 54, 232–239. [Google Scholar] [CrossRef]
- Checinska Sielaff, A.; Urbaniak, C.; Mohan, G.B.M.; Stepanov, V.G.; Tran, Q.; Wood, J.M.; Minich, J.; McDonald, D.; Mayer, T.; Knight, R.; et al. Characterization of the Total and Viable Bacterial and Fungal Communities Associated with the International Space Station Surfaces. Microbiome 2019, 7, 50. [Google Scholar] [CrossRef]
- Godard, B. Allergy and Hypersensitivity Diseases in Space: Physiological Changes, Clinical Aspects, and Mechanisms with Countermeasures. J. Allergy Hypersensitivity Dis. 2024, 2, 100007. [Google Scholar] [CrossRef]
- Crabbé, A.; Nielsen-Preiss, S.M.; Woolley, C.M.; Barrila, J.; Buchanan, K.; McCracken, J.; Inglis, D.O.; Searles, S.C.; Nelman-Gonzalez, M.A.; Ott, C.M.; et al. Spaceflight Enhances Cell Aggregation and Random Budding in Candida Albicans. PLoS ONE 2013, 8, e80677. [Google Scholar] [CrossRef] [PubMed]
- Daudu, R.; Parker, C.W.; Singh, N.K.; Wood, J.M.; Debieu, M.; O’Hara, N.B.; Mason, C.E.; Venkateswaran, K. Draft Genome Sequences of Rhodotorula Mucilaginosa Strains Isolated from the International Space Station. Microbiol. Resour. Announc. 2020, 9, e00570-20. [Google Scholar] [CrossRef] [PubMed]
- Cordero, R.J.B.; Dragotakes, Q.; Friello, P.J.; Casadevall, A. Melanin Protects Cryptococcus Neoformans from Spaceflight Effects. Env. Microbiol. Rep. 2022, 14, 679–685. [Google Scholar] [CrossRef] [PubMed]
- Kim, E.; Panzella, L.; Napolitano, A.; Payne, G.F. Redox Activities of Melanins Investigated by Electrochemical Reverse Engineering: Implications for Their Roles in Oxidative Stress. J. Investig. Dermatol. 2020, 140, 537–543. [Google Scholar] [CrossRef]
- Sun, R.L.; Jones, D.B.; Wilhelmus, K.R. Clinical Characteristics and Outcome of Candida Keratitis. Am. J. Ophthalmol. 2007, 143, 1043–1045. [Google Scholar] [CrossRef]
- Hassan, H.M.J.; Papanikolaou, T.; Mariatos, G.; Hammad, A.; Hassan, H. Candida Albicans Keratitis in an Immunocompromised Patient. Clin. Ophthalmol. 2010, 4, 1211–1215. [Google Scholar] [CrossRef]
- Su, Y.; Liang, Q.; Su, G.; Wang, N.; Baudouin, C.; Labbé, A. Spontaneous Eye Blink Patterns in Dry Eye: Clinical Correlations. Investig. Ophthalmol. Vis. Sci. 2018, 59, 5149–5156. [Google Scholar] [CrossRef]
- Ameeduzzafar; Imam, S.S.; Bukhari, S.N.A.; Ali, A. Preparation and Evaluation of Novel Chitosan: Gelrite Ocular System Containing Besifloxacin for Topical Treatment of Bacterial Conjunctivitis: Scintigraphy, Ocular Irritation and Retention Assessment. Artif. Cells Nanomed. Biotechnol. 2018, 46, 959–967. [Google Scholar] [CrossRef]
- Bravo-Osuna, I.; Vicario-de-la-Torre, M.; Andrés-Guerrero, V.; Sánchez-Nieves, J.; Guzmán-Navarro, M.; de la Mata, F.J.; Gómez, R.; de Las Heras, B.; Argüeso, P.; Ponchel, G.; et al. Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration. Mol. Pharm. 2016, 13, 2966–2976. [Google Scholar] [CrossRef]
- Alvarez-Rivera, F.; Fernández-Villanueva, D.; Concheiro, A.; Alvarez-Lorenzo, C. α-Lipoic Acid in Soluplus(®) Polymeric Nanomicelles for Ocular Treatment of Diabetes-Associated Corneal Diseases. J. Pharm. Sci. 2016, 105, 2855–2863. [Google Scholar] [CrossRef]
- Euliss, L.E.; DuPont, J.A.; Gratton, S.; DeSimone, J. Imparting Size, Shape, and Composition Control of Materials for Nanomedicine. Chem. Soc. Rev. 2006, 35, 1095. [Google Scholar] [CrossRef] [PubMed]
- Abourehab, M.A.S.; Pramanik, S.; Abdelgawad, M.A.; Abualsoud, B.M.; Kadi, A.; Ansari, M.J.; Deepak, A. Recent Advances of Chitosan Formulations in Biomedical Applications. Int. J. Mol. Sci. 2022, 23, 10975. [Google Scholar] [CrossRef] [PubMed]
- Chaplot, S.P.; Rupenthal, I.D. Dendrimers for Gene Delivery—A Potential Approach for Ocular Therapy? J. Pharm. Pharmacol. 2014, 66, 542–556. [Google Scholar] [CrossRef]
- Aksungur, P.; Demirbilek, M.; Denkbaş, E.B.; Vandervoort, J.; Ludwig, A.; Unlü, N. Development and Characterization of Cyclosporine A Loaded Nanoparticles for Ocular Drug Delivery: Cellular Toxicity, Uptake, and Kinetic Studies. J. Control Release 2011, 151, 286–294. [Google Scholar] [CrossRef]
- Carneiro, G.; Silva, E.L.; Pacheco, L.A.; Souza-Fagundes, E.M.; Corrêa, N.C.R.; Goes, A.M.; Oliveira, M.C.; Ferreira, L.A.M. Formation of Ion Pairing as an Alternative to Improve Encapsulation an d Anticancer Activity of All-Trans Retinoic Acid Loaded in Solid Lipid Nanoparticles. Int. J. Nanomed. 2012, 7, 6011–6020. [Google Scholar] [CrossRef]
- Vandervoort, J.; Ludwig, A. Ocular Drug Delivery: Nanomedicine Applications. Nanomedicine 2007, 2, 11–21. [Google Scholar] [CrossRef]
- De Hoon, I.; Barras, A.; Swebocki, T.; Vanmeerhaeghe, B.; Bogaert, B.; Muntean, C.; Abderrahmani, A.; Boukherroub, R.; De Smedt, S.; Sauvage, F.; et al. Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties. ACS Appl. Mater. Interfaces 2023, 15, 3760–3771. [Google Scholar] [CrossRef]
- Alvarez-Lorenzo, C.; Vivero-Lopez, M.; Concheiro, A. Contact Lenses That Transform Gold into Nanoparticles for Prophylaxis of Light-Related Events and Photothermal Therapy. Int. J. Pharm. 2023, 641, 123048. [Google Scholar] [CrossRef]
- Ax, T.; Ganse, B.; Fries, F.N.; Szentmáry, N.; de Paiva, C.S.; March de Ribot, F.; Jensen, S.O.; Seitz, B.; Millar, T.J. Dry Eye Disease in Astronauts: A Narrative Review. Front. Physiol. 2023, 14, 1281327. [Google Scholar] [CrossRef]
- Ong, J.; Mader, T.; Gibson, C.R.; Suh, A.; Panzo, N.; Memon, H.; Lee, R.; Soares, B.; Waisberg, E.; Sampige, R.; et al. The Ocular Surface during Spaceflight: Post-Mission Symptom Report, Extraterrestrial Risks, and in-Flight Therapeutics. Life Sci. Space Res. 2025, 46, 169–186. [Google Scholar] [CrossRef]
- Memon, H.; Ong, J.; Waisberg, E.; Panzo, N.; Sarker, P.; Zaman, N.; Tavakkoli, A.; Lee, A.G. Biophysics of Ophthalmic Medications During Spaceflight: Principles of Ocular Fluid Dynamics and Pharmacokinetics in Microgravity. Life Sci. Space Res. 2024, 42, 53–61. [Google Scholar] [CrossRef] [PubMed]
- Crucian, B.E.; Makedonas, G.; Sams, C.F.; Pierson, D.L.; Simpson, R.; Stowe, R.P.; Smith, S.M.; Zwart, S.R.; Krieger, S.S.; Rooney, B.; et al. Countermeasures-Based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation Onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine. Neurosci. Biobehav. Rev. 2020, 115, 68–76. [Google Scholar] [CrossRef] [PubMed]
- Ammar, H.O.; Salama, H.A.; Ghorab, M.; Mahmoud, A.A. Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride. AAPS PharmSciTech 2009, 10, 808–819. [Google Scholar] [CrossRef] [PubMed]
- Alshaer, W.; Hillaireau, H.; Vergnaud, J.; Ismail, S.; Fattal, E. Functionalizing Liposomes with Anti-CD44 Aptamer for Selective Targeti Ng of Cancer Cells. Bioconjugate Chem. 2015, 26, 1307–1313. [Google Scholar] [CrossRef]
- Liu, D.; Wu, Q.; Chen, W.; Lin, H.; Zhu, Y.; Liu, Y.; Liang, H.; Zhu, F. A Novel FK506 Loaded Nanomicelles Consisting of Amino-Terminated Poly(Ethylene Glycol)-Block-Poly(D,L)-Lactic Acid and Hydroxypropyl Methylcellulose for Ocular Drug Delivery. Int. J. Pharm. 2019, 562, 1–10. [Google Scholar] [CrossRef]
- Abdi, B.; Mofidfar, M.; Hassanpour, F.; Kirbas Cilingir, E.; Kalajahi, S.K.; Milani, P.H.; Ghanbarzadeh, M.; Fadel, D.; Barnett, M.; Ta, C.N.; et al. Therapeutic Contact Lenses for the Treatment of Corneal and Ocular Surface Diseases: Advances in Extended and Targeted Drug Delivery. Int. J. Pharm. 2023, 638, 122740. [Google Scholar] [CrossRef]
- Arora, R.; Jain, S.; Monga, S.; Narayanan, R.; Raina, U.K.; Mehta, D.K. Efficacy of Continuous Wear PureVision Contact Lenses for Therapeutic Use. Contact Lens Anterior Eye 2004, 27, 39–43. [Google Scholar] [CrossRef]
- Andrade, L.M.; Rocha, K.A.D.; De Sá, F.A.P.; Marreto, R.N.; Lima, E.M.; Gratieri, T.; Taveira, S.F. Voriconazole-Loaded Nanostructured Lipid Carriers for Ocular Drug Delivery. Cornea 2016, 35, 866–871. [Google Scholar] [CrossRef]
- Niu, P.; Wu, Y.; Zeng, F.; Zhang, S.; Liu, S.; Gao, H. Development of Nanodrug-Based Eye Drops with Good Penetration Properties and ROS Responsiveness for Controllable Release to Treat Fungal Keratitis. NPG Asia Mater. 2023, 15, 1–15. [Google Scholar] [CrossRef]
- Mader, T.H.; Gibson, C.R.; Pass, A.F.; Kramer, L.A.; Lee, A.G.; Fogarty, J.; Tarver, W.J.; Dervay, J.P.; Hamilton, D.R.; Sargsyan, A.; et al. Optic Disc Edema, Globe Flattening, Choroidal Folds, and Hyperopic Shifts Observed in Astronauts after Long-Duration Space Flight. Ophthalmology 2011, 118, 2058–2069. [Google Scholar] [CrossRef]
- Lee, A.G.; Tarver, W.J.; Mader, T.H.; Gibson, C.R.; Hart, S.F.; Otto, C.A. Neuro-Ophthalmology of Space Flight. J. Neuro-Ophthalmol. 2016, 36, 85. [Google Scholar] [CrossRef] [PubMed]
- Kumar, R.; Waisberg, E.; Ong, J.; Paladugu, P.; Amiri, D.; Saintyl, J.; Yelamanchi, J.; Nahouraii, R.; Jagadeesan, R.; Tavakkoli, A. Artificial Intelligence-Based Methodologies for Early Diagnostic Precision and Personalized Therapeutic Strategies in Neuro-Ophthalmic and Neurodegenerative Pathologies. Brain Sci. 2024, 14, 1266. [Google Scholar] [CrossRef] [PubMed]
- Whitson, P.A.; Charles, J.B.; Williams, W.J.; Cintron, N.M. Changes in Sympathoadrenal Response to Standing in Humans after Spaceflight. J. Appl. Physiol. 1995, 79, 428–433. [Google Scholar] [CrossRef] [PubMed]
- Vallejo, R.; Quinteros, D.; Gutiérrez, J.; Martínez, S.; Rodríguez Rojo, S.; Ignacio Tártara, L.; Palma, S.; Javier Arias, F. Acetazolamide Encapsulation in Elastin like Recombinamers Using a Supercritical Antisolvent (SAS) Process for Glaucoma Treatment. Int. J. Pharm. 2024, 657, 124098. [Google Scholar] [CrossRef]
- Zhang, W.; Liu, L.; Chen, H.; Hu, K.; Delahunty, I.; Gao, S.; Xie, J. Surface Impact on Nanoparticle-Based Magnetic Resonance Imaging Contrast Agents. Theranostics 2018, 8, 2521–2548. [Google Scholar] [CrossRef]
- da Silva, P.H.R.; de Castro, M.A.; Ribeiro, M.C.S.; Gonçalves, L.T.A.; de Melo, L.A.; Freitas-Marques, M.B.; Pedrosa, T.A.; Pianetti, G.A.; Fialho, S.L.; Yoshida, M.I.; et al. Acetazolamide-Loaded Intravitreal Implants for the Treatment of Glaucoma: Formulation, Physicochemical Characterization and Assessment of in Vitro and in Vivo Safety. Int. J. Pharm. 2025, 674, 125507. [Google Scholar] [CrossRef]
Feature | Bacterial Keratitis (Earth) | Bacterial Keratitis (Spaceflight) | Viral Keratitis (Earth) | Viral Keratitis (Spaceflight) | Fungal Keratitis (Earth) | Fungal Keratitis (Spaceflight) |
---|---|---|---|---|---|---|
Immune Response | Rapid innate and neutrophilic response | Impaired immunity, reduced neutrophil function | Cell-mediated immunity controls HSV | T cell suppression may prolong/reactivate virus | Granulomatous inflammation | Impaired macrophage function |
Tear Film Defense | Normal antimicrobial peptides, lysozyme | Reduced tear turnover, compromised defense peptides | Adequate tear-based viral inhibition | Decreased mucin, lysozyme activity | Tear defenses resist fungal invasion | Compromised tear barrier |
Pathogen Virulence | Well-characterized strains; localized infections | Potential increase in virulence (space radiation, stress) | Herpesviruses show latency/reactivation patterns | Reactivation is more likely due to immune dysregulation | Geographic fungi cause trauma-related infection | Unknown pathogenicity in space environment |
Ocular Surface Integrity | Intact epithelial renewal | Microgravity reduces epithelial repair rate | Reactivation often at corneal periphery | Healing delayed in microgravity | Epithelial barrier maintains resistance | Barrier integrity reduced |
Clinical Presentation Risk | Predictable based on exposure | Risk increases due to unpredictable microbe behavior | Controlled unless immunocompromised | Higher likelihood of recurrence | Rare, trauma-induced | Possibly more severe or persistent |
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Lee, R.; Kumar, R.; Shah, J.; Ong, J.; Waisberg, E.; Tavakkoli, A. Tear Film and Keratitis in Space: Fluid Dynamics and Nanomedicine Strategies for Ocular Protection in Microgravity. Pharmaceutics 2025, 17, 847. https://doi.org/10.3390/pharmaceutics17070847
Lee R, Kumar R, Shah J, Ong J, Waisberg E, Tavakkoli A. Tear Film and Keratitis in Space: Fluid Dynamics and Nanomedicine Strategies for Ocular Protection in Microgravity. Pharmaceutics. 2025; 17(7):847. https://doi.org/10.3390/pharmaceutics17070847
Chicago/Turabian StyleLee, Ryung, Rahul Kumar, Jainam Shah, Joshua Ong, Ethan Waisberg, and Alireza Tavakkoli. 2025. "Tear Film and Keratitis in Space: Fluid Dynamics and Nanomedicine Strategies for Ocular Protection in Microgravity" Pharmaceutics 17, no. 7: 847. https://doi.org/10.3390/pharmaceutics17070847
APA StyleLee, R., Kumar, R., Shah, J., Ong, J., Waisberg, E., & Tavakkoli, A. (2025). Tear Film and Keratitis in Space: Fluid Dynamics and Nanomedicine Strategies for Ocular Protection in Microgravity. Pharmaceutics, 17(7), 847. https://doi.org/10.3390/pharmaceutics17070847