Chronic Dry Eye Disease Pathophysiology
Laura Periman, MD
#OnlyYouCanPreventForestFires
#MountainLionsWolvesGrizzlyBears – Part IV
Originally Published on Ophthalmology Management
Part III: Ocular Surface Disease as seen through lessons learned on the Montana Ranch.
Part IV: Pathophysiology of Ocular Surface Disease as seen through lessons learned on the Montana ranch.
Rocky mountain ecosystems can be fragile or robust and are at the mercy of wild swings in climate. So it is on the 160 acres of land my great grandparents homesteaded in the early 1900s, five miles outside of modern day Drummond, Montana (a “blink” of a cowtown—if you blink, you’ll miss it) along I-90. The hand-built homestead stands to this day (photo). Still, a healthy system can endure harsh conditions and return to balance as long as there is care, time and resources to recover. So it is with a healthy Ocular Surface.
My great-grandparents’ homestead in Drummond, MT.
Initiation
#TinderAndKindling
Innate immunity and TLRs (Toll Like Receptors) are the first responders to invaders, ready to quickly fight off bacteria, virus, fungus etc. It’s a good mechanism for responding to the harsh conditions and a healthy ocular surface can return to homeostasis. But these initiating events can also be triggered (aberrantly activated) by hyperosmolarity. Every ecosystem critter and flora has a complex and interdependent role in maintaining the ecosystem diversity and balance. Sometimes it is helpful to know the proper names of big things in the ecosystem such as Puma concolor (mountain lion), Canis lupus (wolf) or Ursus arctos(grizzly bear). So it is with the big things in ocular surface immune cells and cytokines. When immunoregulatory goblet cells and immunoregulatory cytokines such as IL-10 and TGF-B decline, it’s as if the rains stopped coming in the mid-July heat.
Amplification
#WhenAMatchIsStruck
All that drying out isn’t good when headed into thunderstorm season. Loss of immunoregulation means more TLR activation and more acute phase cytokines IL-1 and TNF are produced which up-regulate ICAM-1 expression and also flush out the resident dendritic cells like spooked grouse that then fly to the nearest lymph node.
Recruitment
#JumpTheRiver
The activated dendritic cells arrive in the local-regional lymph node and recruit Th1 and Th17 cells. These enter the circulatory system and target the distressed ecosystem (via LFA-1:ICAM-1 interactions) like invasive plants taking root to the pasture lands. The Th1 and Th17 cells then adhere to ICAM-1 expressing epithelial and conjunctival cells as well as activated dendritic cells. (T-cell cytokine release occurs via dual activation by ICAM-1:LFA-1 and MHCII:TCR interactions). The resulting cytokine release (including goblet-cell-killing IFN-gamma and epithelial-cell-tight-junction-weakening MMP9) is like the seed pod scatter of spotted knapweed, which will result in more damage. My rancher grandpa detested the invasive, ecosystem-balance-destroying spotted knapweed.
Chronic Self-Perpetuation and Damage
#ForestFire
Now the heat from the grass fire dries out the moisture that’s left from the shrubs and trees, creating more tinder for the fire (TLR activation). With progressive loss of immunoregulatory goblet cells, the fire picks up intensity and involves more area (more triggered dendritic cells). If left unattended, this vicious circle keeps going on unchecked and pretty soon you have a full-fledged forest fire. In the case of autoimmune disease, you’re fighting a forest fire with high winds fanning the flames. The best time to control the damage has past, and the work is much harder now. But, if you dig in with all you’ve got, maybe the homestead can be spared and even restored.
The entire TFOS DEWS II report is available to all for free at www.TearFilm.org.
Laura M. Periman, MD is Director of Dry Eye Services and Clinical Research at Evergreen Eye Center in Seattle, WA. Relevant to this series, she discloses relationships with Allergan, Bio-Tissue, Eyedetec, Lumenis, Science Based Health, Sun Pharmaceuticals, TearLab, Topcon and Visant.