Our objective in this study was to analyze the aberrant neural regeneration activity
in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus
patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus
patients and 29 age-matched healthy control subjects. Corneal nerve fiber density
(CNFD, the number of fibers/mm2) and peripheral Langerhans cell morphology were lower
(p < 0.05) in systemic lupus erythematosus patients compared to the control group.
Interestingly, corneal nerve branch density, corneal nerve fiber length, corneal nerve
fiber total branch density, and corneal nerve fiber area showed a negative correlation
with disease duration. A negative correlation was also demonstrated between average
corneal nerve fiber density and central Langerhans cell density. This is in line with
our hypothesis that corneal somatosensory terminal Piezo2 channelopathy-induced impaired
Piezo2–Piezo1 crosstalk not only disrupts regeneration and keeps transcription activated,
but could lead to Piezo1 downregulation and cell activation on Langerhans cells when
we consider a chronic path. Hence, Piezo2 containing mechanosensory corneal nerves
and dendritic Langerhans cells could also be regarded as central players in shaping
the ocular surface neuroimmune homeostasis through the Piezo system. Moreover, lost
autoimmune neuroinflammation compensation, lost phagocytic self-eating capacity, and
lost transcription regulation, not to mention autoantibodies against vascular heparin
sulfate proteoglycans and phospholipids, could all contribute to the progressive fashion
of dry eye disease in systemic lupus erythematosus.
