Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion

Abstract

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.

Keywords: Langerhans cell; Piezo1; Piezo2; autoimmune disease; channelopathy; dry eye disease; systemic lupus erythematosus.

Figure 1

In vivo confocal corneal microscopic records in a healthy control eye (A) and in an eye of a patient with SLE and dry eye (B). The density and thickness of subepithelial nerve plexi (arrow) and the number of branches (arrowhead) are reduced in SLE compared to normal eyes. Langerhans cells are present in SLE (empty arrow). The same scale bar is applicable to Figure 1A,B.

Figure 2

Correlation of CNFD and central LCD.

Figure 3

Correlation of CNBD with disease duration (r = −0.389; p = 0.040).

Figure 4

Correlation of CNFL with disease duration (r = −0.399; p = 0.035).

Figure 5

Correlation of CTBD with disease duration (r = −0.415; p = 0.028).

Figure 6

Correlation of CNFA with disease duration (r = −0.480; p = 0.010).