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Source: Thailand Medical News  Dec 09, 2019
‘Probiotic Drops’ For Future Treatments Of Eye Diseases? ….An Intro To The Eye Microbiome
‘Probiotic Drops’ For Future Treatments Of Eye Diseases? ….An Intro To The Eye Microbiome
Source: Thailand Medical News  Dec 09, 2019
Many of you may be familiar with the newly found fact that your gut and skin are home to a collection of microbes ranging from fungi, bacteria and viruses, that are vital for keeping you healthy. But how many of you are aware that your eyes are also host a unique menagerie of microbes? Collectively, they are called  the eye microbiome. It has been discovered that when these microbes are out of balance, ie either too much or too few of certain types, a variety of eye diseases may emerge. Ophthalmologists and medical researchers these days are intrigued by the eye microbiome. In this specially curated article, Thailand Medical News gives you a basic introduction to the eye microbiome.


 
A past study1 showed bacteria live on the surface of the eye and stimulating protective immunity. Medical researchers are now beginning to discover the microbial factors that can be exploited to create innovative therapies for a range of eye disorders like Dry Eye Disease, Sjogren's Syndrome and corneal scarring. Soon it may be possible to engineer bacteria to treat eye diseases in humans.
 
Eye Microbiome
 
Often, when discussing the microbiome, most medical professionals usually think of the gut, and deservedly so; researchers think one colon can harbor more than 10 trillion bacteria. That being said, more attention is now being focused on the impact microbiomes have at other sites, including the skin, and areas with very few bacteria, like the lungs, vagina and eyes.
 
In the last few years, the role of the eye microbiome in ocular health was controversial2. Scientists believed that healthy eyes lacked an organized microbiome. Studies showed that bacteria from the air, hands or eyelid margins could be present on the eye; however, many believed these microbes were simply killed or washed away by the continual flow of tears.
 
However, due to recent studies, medical researchers have concluded that the eye does, indeed, harbor a "core" microbiome that appears dependent on age, geographic region, ethnicity, contact lens wear3 and state of disease. The "core" is limited to four genera of bacteria StaphylococciDiphtheroidsPropionibacteria, and Streptococci. In addition to these bacteria4, torque teno virus, implicated in some intraocular diseases, also counts as a member of the core microbiome as it is present on the surface of the eye of 65% of healthy individuals.
 
The findings suggests that ophthalmologists and doctors should think more deeply about the risks and benefits to the eye microbiome when prescribing antibiotics. The antibiotics may kill bacteria that are providing a benefit to the eye. The same goes for eye steroids.
 
In a new study spanning more than a decade and including more than over 340,000 patients in the U.S., the authors found that antibiotics were used to treat 60% of acute conjunctivitis5 (pink eye) cases. But viral infections are the most likely causes of pink eye, and not treatable with antibiotics. More striking, even cases caused by bacteria often resolve in 7 to 10 days without intervention. It is well known that excessive or inappropriate antibiotic use can disrupt the eye microbiome, leading to infection7, autoimmunity8 and even cancer9.
 
In the last few years, studies assessing the eye microbiome and disease have boomed. They've generated an immense amount of data, but most of it is correlative. This means that certain bacteria have been linked to certain diseases, like Sjogren's6 Syndrome or bacterial keratitis10. However, whether these bacteria are causing these diseases is still unknown.
 
Ocular immunologist Dr Rachel Caspi in 2016, at the National Eye Institute hypothesized that protective bacteria were living near or on the eye. Indeed,it was found a resident bacterium, Corynebacterium mastitidis (C. mast), that stimulates immune cells to produce and release antimicrobial factors that kill harmful microbes into the tears.
 
Through a series of experiments, the Caspi lab was able to show for the first time a causal relationship11 between C. mast and a protective immune response. Whenever C. mast was present on the eye surface, mice were more resistant to two species of bacteria known to cause blindness: Candida albicans and Pseudomonas aeuruginosa12.


 
Researchers and ophthalmologists are also at the moment working to genetically engineer eye-colonizing bacteria to act as long-term delivery vehicles to the surface of the eye as new "prob-eye-otic" therapies that would act to secrete immune regulating factors, which would limit symptoms associated with conditions like Dry Eye Disease, which affects around 4 million people in the U.S. per year.  Its only a matter of time before it will  just squirting eye drops into your dry eyes, that contain bacteria that will colonize your eye and secrete the lubricants and other factors your body is missing.
 
References:

1.  An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells, Anthony J. St. Leger, Jigar V. Desai, Rebecca A. Drummond ,Yoichiro Iwakura, Michail S. Lionakis, Rachel R. Caspi 5 July 11 2017DOI:https://doi.org/10.1016/j.immuni.2017.06.014
 
2. Characterization of the normal microbiota of the ocular surface
Mark D.P.Willcox
https://doi.org/10.1016/j.exer.2013.06.003
 
3. Changes in the Eye Microbiota Associated with Contact Lens Wearing
Hakdong Shin, Kenneth Price, Luong Albert, Jack Dodick, Lisa Park, Maria Gloria Dominguez-Bello
Janet K. Jansson, Editor
DOI: 10.1128/mBio.00198-16
 
4. Paucibacterial Microbiome and Resident DNA Virome of the Healthy Conjunctiva
Thuy DoanLakshmi AkileswaranDallin AndersenBenjamin JohnsonNarae KoAngira ShresthaValery ShestopalovCecilia S. LeeAaron Y. LeeRussell N. Van Gelder
Investigative Ophthalmology & Visual Science October 2016, Vol.57, 5116-5126. doi:https://doi.org/10.1167/iovs.16-19803
 
5. Antibiotic Prescription Fills for Acute Conjunctivitis among Enrollees in a Large United States Managed Care Network
Presented at: American Ophthalmological Society 152nd Annual Meeting, May 2016, Colorado Springs, Colorado; Association for Research in Vision and Ophthalmology Annual Meeting, May 2016, Seattle, Washington.
Nakul S. Shekhawat, MD, MPH1,2Roni M. Shtein, MD1,2Taylor S. Blachley, MS1,2Joshua D. Stein, MD, MS1,2,3,∗,  DOI: https://doi.org/10.1016/j.ophtha.2017.04.034
 
6. de Paiva, C., Jones, D., Stern, M. et al. Altered Mucosal Microbiome Diversity and Disease Severity in Sjögren Syndrome. Sci Rep 6, 23561 (2016) DOI : https://doi.org/10.1038/srep23561
 
7. Role of the Microbiota in Immunity and Inflammation
DOI:https://doi.org/10.1016/j.cell.2014.03.011
Yasmine Belkaid, Timothy W. Hand
 
8. Antibiotics and autoimmune and allergy diseases: Causative factor or treatment?
AnnaStrzępaaFrancis M.Lobob,MonikaMajewska-Szczepanika,MarianSzczepanika
https://doi.org/10.1016/j.intimp.2018.10.021
 
9. The role of the microbiota in inflammation, carcinogenesis, and cancer therapy
Amiran Dzutsev ,Romina S. Goldszmid ,Sophie Viaud ,Laurence Zitvogel ,Giorgio Trinchieri
First published: 18 October 2014, https://doi.org/10.1002/eji.201444972
 
10. Impact of Microbiota on Resistance to Ocular Pseudomonas aeruginosa-Induced Keratitis
Abirami Kugadas,Stig Hill Christiansen, Saiprasad Sankaranarayanan, Neeraj K. Surana, Stefanie Gauguet, Ryan Kunz, Raina Fichorova, Thomas Vorup-Jensen, Mihaela Gadjeva 
Published: September 22, 2016https://doi.org/10.1371/journal.ppat.1005855
 
11. An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells, Anthony J. St. Leger, Jigar V. Desai,Rebecca A. Drummond, Yoichiro Iwakura, Michail S. Lionakis, Rachel R. Caspi 5 July 11, 2017 DOI:https://doi.org/10.1016/j.immuni.2017.06.014
 
12. An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells, Anthony J. St. Leger, Jigar V. Desai, Rebecca A. Drummond, Yoichiro Iwakura
Michail S. Lionakis, Rachel R. Caspi 5,
Published:July 11, 2017DOI:https://doi.org/10.1016/j.immuni.2017.06.014