Original articles
Photoreceptor apoptosis in human retinal detachment

https://doi.org/10.1016/j.ajo.2004.11.046Get rights and content

Purpose

Although photoreceptor cell apoptosis has been demonstrated in various animal models of retinal detachment (RD), little is known about its occurrence in human RD. We sought to determine whether human photoreceptor cells undergo apoptosis in response to primary and recurrent RD.

Design

Prospective, clinical-pathologic, case series.

Methods

Retinal tissue fragments excised during the course of vitreous surgery for RD and recurrent RD were frozen, cut into 4-μm sections, and analyzed using a TdT-dUTP terminal nick-end labeling assay for cell apoptosis. The onset of patient symptoms was used to estimate the duration of the RD.

Results

There were eight patients with primary RD and four patients with recurrent RD enrolled in this study. Duration of RD ranged from 1 to 180 days in the primary RD group, and 2 to 15 days in the recurrent RD group. All retinal tissue specimens had TUNEL-positive cells localized to the outer nuclear layer of the retina, consistent with the localization of photoreceptor cell bodies. TUNEL-positive cells were first identified at 24 hours, peaked by 2 days, and dropped to a low level by 7 days after RD. Recurrent RD induced a greater number of TUNEL-positive cells/mm2 in the ONL compared with primary RD at corresponding timepoints after the onset of RD.

Conclusions

In response to primary and recurrent RD, human photoreceptor cells follow a pattern of apoptosis that is similar to that seen in animal models of RD. This study suggests that photoreceptor cell apoptosis may be one of the causes of reduced vision after RD, especially those that involve the macula. Drugs that inhibit photoreceptor apoptosis may help improve the final visual prognosis of patients with RD.

Section snippets

Methods

Patients who were undergoing a vitrectomy for primary or recurrent RD repair were invited to participate in this study and were asked to sign the Massachusetts Eye & Ear Infirmary IRB-approved informed consent form. Patient demographic and clinical information was obtained and recorded. The date of the first acute retinal symptom, such as photopsias or new onset of floaters, was recorded and used to estimate the age of the retinal tear/RD.

Retinal tissue fragments (flap of horseshoe retinal tear

Results

The study group contained eight primary RD and four recurrent RD patients. Patient characteristics at the time of the initial RD are summarized in Table 1 and Table 2, respectively. Patient age ranged from 13 to 68 (average, 42.2 years).

Primary RDs were associated with trauma (three cases), giant retinal tears (three cases), choroidals after cataract surgery (one case), or were idiopathic (one case) (Table 1). Duration of RD ranged from 1 to 180 days. Recurrent RD occurred from 4 to 8 weeks

Discussion

In the present study, we report that human photoreceptor cells undergo apoptosis in response to primary and recurrent RD. The time course of photoreceptor cell apoptosis with respect to the duration of RD parallels the findings in animal models of RD, namely, apoptosis was identified within 24 hours, peaked at day 2, and dropped down to a low level after day 7. Moreover, we discovered that photoreceptor apoptosis reached a higher level in recurrent RD than in primary RD, a finding that has not

Dr. Jorge Arroyo is the Director of the Retina Service at Beth Israel Deaconess Medical Center/Harvard Medical School. His clinical interests include macular degeneration, retinal degeneration, and ocular trauma. He is the principal director of the Longwood Macular Translocation Surgery Program and is studying the benefits and risks of 360-degree macular translocation surgery for patients with severe wet AMD.

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    However, recent evidence from our group and others suggests that RRDs should be repaired within 3 days of macular detachment or presentation (Figueiredo et al., 2021a; Henrich et al., 2009; Sothivannan et al., 2022; Yorston et al., 2021). When the retina is detached, the photoreceptors lose their tightly regulated homeostasis (Cook et al., 1995; Arroyo et al., 2005). It is intuitive that restoring this homeostasis as soon as possible is likely to lead to the best anatomic and functional outcomes for patients.

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Dr. Jorge Arroyo is the Director of the Retina Service at Beth Israel Deaconess Medical Center/Harvard Medical School. His clinical interests include macular degeneration, retinal degeneration, and ocular trauma. He is the principal director of the Longwood Macular Translocation Surgery Program and is studying the benefits and risks of 360-degree macular translocation surgery for patients with severe wet AMD.

Dong Feng Chen, M.D., Ph.D., Assistant Scientist at the Schepens Eye Research Institute; Assistant Professor at the Department of Ophthalmology, Program in Neuroscience, Harvard Medical School. Dr. Chen is a neurobiologist, particularly interested in the regeneration and repair of the retina and optic nerve. Dr. Chen’s work has been focused on the understanding of molecular mechanisms controlling retinal neural development and optic nerve regeneration.

Dr. Arroyo is a recipient of a NIH K-23 Mentored Patient-Oriented Research Career Development Award.

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