Abstract：
The study aims to characterize the robustness of distinct clinical assessments in identifying the underlying conditions of dry eye disease (DED), with a specific emphasis on the involvement of conjunctival goblet cells.
Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination.
Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED.
The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED.
Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination.
Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED.
The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED.
摘要：
■该研究旨在表征不同临床评估在确定干眼病（DED）的潜在条件的稳健性，特别强调结膜杯状细胞的参与。
■七只接受手术切除泪腺和Harderian腺的兔子分为两组，一种通过将三氯乙酸（TCA）局部浸泡至球结膜（n=3）而消融结膜杯状细胞，另一种没有（n=4），每周使用Schirmer检验评估DED的条件，撕裂破裂时间（TBUT），泪液渗透压,和国家眼科研究所(NEI)荧光素染色分级。8周后,兔子被处死,并摘除眼睛进行组织病理学检查。
■组织病理学分析显示两组角膜上皮变薄。而TCA浸泡显著降低结膜杯状细胞的密度，没有TCA的DED兔也显示杯状细胞密度部分降低，可能归因于泪腺切除术。两组均显示Schirmer试验和TBUT显著降低,以及泪液渗透压的增加。在用TCA浸泡的DED兔子中，泪液渗透压显著增加，提示泪液渗透压对结膜杯状细胞的丢失和/或功能障碍高度敏感。荧光素染色在两组中逐渐增加，并且相似。这表明荧光染色可能不会显示泪膜的早期破坏，直到DED的长期进展。
■Schirmer试验，TBUT,泪液渗透压,和NEI荧光素分级不同，但互补，用于评估DED的临床评估。通过在确定的DED兔模型中进行这些评估，有或没有结膜杯状细胞消融，强调了这些细胞在泪液渗透压稳态中的作用。在确定DED的潜在条件时表征这些评估的稳健性将指导DED患者更合适的管理。
■七只接受手术切除泪腺和Harderian腺的兔子分为两组，一种通过将三氯乙酸（TCA）局部浸泡至球结膜（n=3）而消融结膜杯状细胞，另一种没有（n=4），每周使用Schirmer检验评估DED的条件，撕裂破裂时间（TBUT），泪液渗透压,和国家眼科研究所(NEI)荧光素染色分级。8周后,兔子被处死,并摘除眼睛进行组织病理学检查。
■组织病理学分析显示两组角膜上皮变薄。而TCA浸泡显著降低结膜杯状细胞的密度，没有TCA的DED兔也显示杯状细胞密度部分降低，可能归因于泪腺切除术。两组均显示Schirmer试验和TBUT显著降低,以及泪液渗透压的增加。在用TCA浸泡的DED兔子中，泪液渗透压显著增加，提示泪液渗透压对结膜杯状细胞的丢失和/或功能障碍高度敏感。荧光素染色在两组中逐渐增加，并且相似。这表明荧光染色可能不会显示泪膜的早期破坏，直到DED的长期进展。
■Schirmer试验，TBUT,泪液渗透压,和NEI荧光素分级不同，但互补，用于评估DED的临床评估。通过在确定的DED兔模型中进行这些评估，有或没有结膜杯状细胞消融，强调了这些细胞在泪液渗透压稳态中的作用。在确定DED的潜在条件时表征这些评估的稳健性将指导DED患者更合适的管理。
