1. New Antiinflammatory Strategy to Treat Murine Dry-Eye Disease
André Okanobo, MD, Mohammad Dastjerdi, MD, Sunil Chauhan, DVM, PhD, Nambi Nallasamy, BS, Zahra Sadrai, MD, Reza Dana, MD, MPH, MSc.
Schepens Eye Research Institute,
Harvard Medical School, Boston, MA
Financial Disclosures :The Schepens Eye Research Institute and Mass. Eye and Ear Infirmary hold rights to the intellectual property for the use of IL-1 blockade in ocular surface disease.
Financial support: Prevent Blindness America and NIH K24EY019098

2. Inflammation and Dry Eye
Dry eye was originally considered to be simply a lack, or diminishment, of tear production
We now know that inflammation plays a critical role in the pathophysiology
This is supported by clinical data using anti-inflammatory therapies which lead to significant amelioration of the signs and symptoms of DED

3. IL-1 and IL-1Receptor Are Upregulated in Dry Eye
Normal
40x
Dry Eye
IL-1R Expression; Cross-Section Cornea Epifluorescent Microscope EP AC

4. Propose
Given that IL-1–mediated mechanisms play a critical role in corneal inflammation, we propose that local blockade of IL-1 may offer a novel approach to the management of dry eye disease

5. Interleukin-1 (IL-1) Proinflammatory forms Anti-inflammatory form
IL-1 receptor antagonist (IL-1Ra)
IL-1R
IL-1R
IL-1
IL-1
IL-1AcP
IL-1AcP
IL-1Ra
Signal
Transduction
Kinase, Phosphatase, etc.

6. Induction of Dry Eye Disease
Controlled Environment Chamber
humidity below 25%
constant temperature of 21-23ºC
airflow of 15 L/minute
Topical atropine and SC scopolamine
Barabino S, et al. The controlled environment chamber: a new mouse model of dry eye. Invest Ophthalmol Vis Sci. 2005;46(8):

7. Topical formulation and treatment regiment
Formulation prepared by MEEI pharmacy
Masked Fashion
Induction of Dry Eye
Treatment
CFS
Control Environment Chamber
DAY
Euthanized
Groups (n=6 eye)
IL-1Ra
CsA
Methylprednisolone
4. Vehicle (1% carboxymethylcellulose)
5. Untreated (no eye drops)
3µl (3x/day)
CFS: Corneal Fluorescein Staining

8. Corneal Staining

9. mRNA expression levels of IL-1β in the cornea

10. Enumeration of macrophages in the cornea

11. IL-1Ra inhibits lymphangiogenesis in dry eye
Normal
LYVE-1(Lymphatics Vessels) / CD31(Blood Vessels)
IL-1Ra 5%

12. Conclusion
IL-1Ra ameliorates dry eye disease comparable to methylprednisolone
Signs: CFS scores were significantly improved
Our data suggests that this is due to the marked inhibition of corneal inflammation:
Down regulated levels of IL-1β mRNA
Reduced infiltration of macrophages
Inhibition of lymphangiogenesis
Thus the use of topical IL-1Ra appears to be a promising therapeutic modality to dry eye disease and possibly in other inflammatory conditions of the cornea and ocular surface